|
||||||||||||||||
|
||||||||||||||||
|
||||||||||||||||
|
| ||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||
Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 91
B
Commissioned Paper: Comparison of
Immunity to Pathogens in Humans,
Chimpanzees, and Macaques
The following paper was commissioned by the Committee on the Use of
Chimpanzees in Biomedical and Behavioral Research. The responsibility
for the content of this paper rests with the authors and does not neces-
sarily represent the views of the Institute of Medicine or its committees
and convening bodies.
By: Nancy L. Haigwood, Ph.D.
Professor of Microbiology and Immunology
Director
Oregon National Primate Research Center
Christopher M. Walker, Ph.D.
Professor of Pediatrics
Nationwide Children’s Hospital
The Ohio State University
91
OCR for page 92
92 ASSESSING THE NECESSITY OF THE CHIMPANZEE
INTRODUCTION
The purpose of this white paper is to compare genetic and functional
features of immunity and the response to infection in humans and major
nonhuman primate species currently used in biomedical research. The
search for appropriate disease models has been stimulated by the need to
understand the most intractable of the persistent and lethal pathogens, as
well as chronic diseases and conditions that are determined by the genet-
ic makeup of the individual. Because the outcome of infection is gov-
erned by carefully coordinated innate and adaptive immune responses,
and pathogens have evolved strategies to evade these defenses, use of
animal models that recapitulate key features of human infection is criti-
cal. Successful nonhuman primate models closely emulate human im-
munity, inflammation, and disease sequelae. They can also provide a
critical pathway to clinical testing of risky prevention or treatment strate-
gies for serious human diseases.
Some past successes of infectious diseases research in nonhuman
primates are described. However, the primary objective of the paper is to
identify conditions that either support or limit use of these animals for
the study of human viral, bacterial, or parasitic infections. A survey of
the published literature reveals that the common chimpanzee (Pan trog-
lodytes) is the only great ape used in infectious disease research. With
few exceptions there is usually no alternative, because lower species are
not permissive for infection or fail to replicate key features of disease.
Most studies involve very small numbers of chimpanzees to ensure safe
translation of vaccines or therapeutics to humans, or provide incontro-
vertible evidence for basic mechanisms of immune control and evasion
that cannot be obtained in human subjects. Various monkey species, pri-
marily the Asian macaques (Macaca species), have served as models for
infection with human viruses and microbes. Alternatively, monkey path-
ogens like the simian immunodeficiency viruses (SIV) provide a reliable
model of human infection with closely related viruses like human immu-
nodeficiency virus (HIV). Infection studies with human and monkey vi-
ruses have facilitated advances in vaccine development and studies of
immunity and pathogenesis relevant to humans.
Sequencing of the human, chimpanzee, and macaque genomes has
provided unprecedented insight into the evolutionary relationship be-
tween these species, especially for genes that regulate host defense and
susceptibility to infection. Here we also provide examples of gene fami-
lies involved in immunity that have been largely conserved since specia-
OCR for page 93
93
APPENDIX B
tion, and others that have undergone rapid evolution because of selective
pressure by infectious diseases. How these adaptive changes might affect
modeling of human infectious diseases in monkeys and great apes is dis-
cussed. Contemporary examples of primate infectious disease models
that replicate most if not all features of human infection and immunity
are provided. Where infection models are not perfectly matched in hu-
mans and nonhuman primates, differences have provided insight into key
features of the relationship between the pathogen and its human host.
Finally, several practical advantages of nonhuman primate models
are also reviewed. The include the ability to (1) infect with clonal or ge-
netically modified pathogens, (2) modify the immune response to identi-
fy protective mechanisms, (3) sample at the earliest times after infection,
often before symptoms are apparent in humans, and (4) access organs or
tissues that are the primary site of infection. The latter is particularly im-
portant because blood, which is often the only compartment available for
human sampling, may not adequately reflect immunity at the site of in-
fection. Advances in adapting the most sophisticated technologies to
nonhuman primates, including methods to monitor immunity, and under-
stand molecular aspects of infection using genomic and proteomic ap-
proaches, has the potential to provide new insight into vaccination and
infection with known and emerging pathogens.
CHIMPANZEES
Historical and Current Examples of Human Infectious Disease
Research in Chimpanzees
Chimpanzees have been used for over 100 years to model human vi-
ral, bacterial, and parasitic infections. This long history has revealed that
chimpanzees are often uniquely permissive for infection with some med-
ically important human pathogens. These animals can also provide a
more faithful model of human disease than lower nonhuman primates.
Studies in chimpanzees, particularly with hepatotropic viruses, have pro-
vided critical insight into host defense mechanisms and facilitated devel-
opment of vaccines that have changed global public health. Yet for other
pathogens key features of immunity and infection outcome differ be-
tween humans and chimpanzees. In these instances, the host-pathogen
interaction is influenced by adaptations that are species-specific despite a
strikingly close genetic relationship.
OCR for page 94
94 ASSESSING THE NECESSITY OF THE CHIMPANZEE
The promise and limitations of chimpanzees as an infectious disease
model were first recognized in a 1904 publication from Albert Grunbaum
who transmitted the Eberth-Gaffky bacillus (Salmonella typhi) to two
animals (Grunbaum, 1904). The bacillus, isolated 10 years earlier, was
the suspected cause of enteric fever. Efforts to satisfy Koch’s third postu-
late by transmission of disease to rats, rabbits, and monkeys had failed.
Infection of chimpanzees was successful, but with much milder disease
symptoms than expected. The author noted “the virulence of my cultures
was not sufficient to produce a fatal result in the two instances in which
they were given the opportunity to do so” (Grunbaum, 1904). That the
chimpanzee might not be suitable for S. typhi vaccine development was
highlighted in a 1914 publication (Nichols, 1914). The author, a propo-
nent of a killed vaccine, critiqued an earlier study where such an ap-
proach had failed. “The authors found that a whole killed vaccine did not
protect chimpanzees. But they used tremendous infecting doses—the
contents of a whole Kolle flask. The problems must be settled, as some
of them already have been settled, by actual experience with large num-
bers of men kept under close observation” (Nichols, 1914).
Infectious disease research involving chimpanzees published in the
last 30-40 years fits into three broad categories. They include (1) identi-
fication and characterization of infectious agents that are serious public
health threats; (2) characterization of protective immunity and how it is
subverted; and (3) development of strategies to prevent or treat human
infections. All published experimental infection studies used human
pathogens and not closely related (and thus potentially different) chim-
panzee pathogens as a model. Here, factors that determine the suitability
of chimpanzees for research on infectious diseases are reviewed. Malar-
ia, respiratory syncytial virus (RSV), HIV, and the hepatitis viruses are
used as case studies.
Malaria
Malaria vaccine research is made difficult by complexities of the
parasite life cycle and selection of antigens to either interrupt transmis-
sion of infection or protect from disease after a mosquito bite (Good and
Doolan, 2010). That irradiated P. falciparum sporozoites prevent disease
was established several decades ago, but this approach is not easily
scaled for human vaccination (Hoffman and Doolan, 2000). A small pilot
study demonstrating protection of chimpanzees by a recombinant liver
stage antigen derived from the sporozoites (Daubersies et al., 2000,
OCR for page 95
95
APPENDIX B
2008) laid the foundation for a recent human clinical trial of this concept
(ClinicalTrials.gov NCT00509158). Nevertheless, malaria is exceptional
because human challenge studies are permissible and studies in lower-
order species can provide guidance for vaccine development. Many ma-
laria trials that are either underway or completed involved parasite chal-
lenge of vaccinated human volunteers followed by co-artemether
eradication therapy if necessary (as an example see Porter et al., 2011).
Recent studies have also included sophisticated analyses of humoral and
cellular immune responses with goal of identifying protective correlates
in human volunteers (Good, 2011). While chimpanzees have been used
sparingly to date, there is increasing concern that no successful vaccine
has emerged from the concepts tested to date. If progress requires identi-
fication of new antigens and a better understanding of immunity, espe-
cially in the liver (Good, 2011), the place of the chimpanzee in malaria
research may be reconsidered.
Chimpanzees have also been critically important for the in vivo gen-
eration of malaria parasites that are recombinants between drug-resistant
and drug-sensitive strains in order to map drug resistance genes and
thereby better understand the metabolism of these pathogens and to de-
velop improved drugs. Several studies that used parasites generated by
this approach have been published recently (Hayton et al., 2008;
Nguitragool et al., 2011; Sa et al., 2009).
Respiratory Syncytial Virus
RSV was first isolated from captive chimpanzees with upper respira-
tory tract disease (Blount et al., 1956) but was quickly identified as a
human virus (Chanock and Finberg, 1957; Chanock et al., 1957). It is
now recognized as the most important viral agent of severe respiratory
tract disease in infants and children worldwide (Hall et al., 2009; Nair et
al., 2010). RSV is also an important cause of morbidity and mortality in
the elderly and in profoundly immunosuppressed individuals. Protection
of vulnerable infants and young children from severe airway disease by a
licensed monoclonal antibody against the RSV F protein, as well as the
protection in the general population afforded by prior infection, suggests
that active vaccination is also feasible (Graham, 2011). Progress over the
past 4 decades was slowed by an unfortunate clinical trial of a formalin
inactivated RSV vaccine that worsened disease and resulted in two
deaths upon natural infection with the virus (Kapikian et al., 1969).
There is a general consensus that the vaccine failed to induce potent neu-
OCR for page 96
96 ASSESSING THE NECESSITY OF THE CHIMPANZEE
tralizing antibody responses, provoked heightened lymphoproliferative
responses, and was associated with eosinophilia and immune complex
deposition in airways. Rodent and monkey models have demonstrated
Th2 responses and eosinophilia using formalin-inactivated vaccines, but
the precise mechanisms of immunopathogenesis remain undefined (re-
viewed in Graham, 2011). With the failure of this killed vaccine, devel-
opment of live-attenuated RSV vaccines was initiated.
Chimpanzees are the only experimental animal in which RSV repli-
cation and pathogenicity approach that of humans. Small numbers of
chimpanzees were used to demonstrate the safety of live-attenuated vac-
cines as well as identifying candidates that were sufficiently attenuated to
move forward into clinical trials (e.g., Clinicaltrials.gov NCT00767416)
(Crowe et al., 1993, 1994; Teng et al., 2000; Whitehead et al., 1999).
Importantly, the body temperature of the chimpanzee is the same as that
of humans. Other available nonhuman primates have higher body tem-
peratures and so chimpanzees are uniquely suited for pre-clinical evalua-
tion of temperature-sensitive vaccine candidates, which comprise all of
the candidates evaluated in clinical trials to date. In addition, the chim-
panzee experiments added to a body of evidence that both live attenuated
vaccines and vectored vaccines are not associated with enhanced disease.
A series of clinical trials have been initiated in infants and young chil-
dren to evaluate safety, attenuation, and immunogenicity of several live
RSV vaccines (for instance, see ClinicalTrials.gov NCT00767416). It is
too soon to know if live RSV vaccines that are sufficiently attenuated to
be well tolerated in young infants (Karron et al., 2005) will be sufficient-
ly immunogenic to prevent severe RSV disease. Alternate approaches
involving recombinant viral vectors (such as attenuated parainfluenza
virus type 3; see ClinicalTrials.gov NCT00686075), virus-like particles
(ClinicalTrials.gov NCT01290419), and subunit proteins are at various
stages of development and evaluation. RSV subunit vaccines are consid-
ered unsuitable for use in RSV-naïve individuals, based on studies in
mice, cotton rats, and African green monkeys. However, the evolutionary
distance relative to humans, reduced permissiveness to RSV replication,
and lack of disease may limit the predictive value of these models
(Graham, 2011). Until the significant medical need for an RSV vaccine is
fully met, it is difficult to exclude the possibility that chimpanzees will be
required to answer questions about mechanisms and duration of immune
protection and disease potentiation.
OCR for page 97
97
APPENDIX B
The Human Immunodeficiency Virus
Susceptibility of chimpanzees to persistent HIV infection was first
reported in 1984, a little more than 1 year after discovery of the virus
(Alter et al., 1984). Successful infection of two animals, and persistence
of lymphadenopathy for several weeks in one of them, suggested that the
chimpanzee would be valuable for further studies of acquired immune
deficiency syndrome (AIDS) (Alter et al., 1985). This study, and all oth-
er early studies of immunity and vaccine development, used viruses like
HIVIIIb and HIVSF2 that adapted in culture to use CXCR4 as a co-receptor
for cell entry. These viruses did initiate infection in chimpanzees, but
viremia was usually low or short-lived and immunodeficiency was not
observed (with one notable exception described below). Several studies
of the early studies with CXCR4 adapted viruses nonetheless provided
insight into the nature of antiviral immunity in infected chimpanzees
(Nara et al., 1987), including the development of neutralizing antibodies
(Prince et al., 1987), proliferative responses, and lack of CD4+ T cell im-
pairment (Eichberg et al., 1987). Important advances were made in un-
derstanding mucosal routes of HIV-1 transmission using chimpanzees
(Fultz et al., 1986), as well as the now better-appreciated issue of
superinfection (Fultz et al., 1987). Some success in protecting animals
from infection with the CXCR4-dependent HIV strains was achieved by
active and passive vaccination. Sterilizing immunity was induced by
immunization with recombinant subunit envelope glycoproteins, but only
with the CXCR4-utilizing virus HIVIIIB matched to the envelope
immunogen (Berman et al., 1988). The vaccine was not fully protective
when a different strain belonging to the same subtype, HIVSF2, was used
(El-Amad et al., 1995). Passive transfer of HIVIG at a higher dose even-
tually showed protection against HIVIIIB (Prince et al., 1991), as did one
of the first neutralizing monoclonal antibodies directed against the HIV
envelope (Emini et al., 1990). The interpretation of vaccine and anti-
body-based protection work in chimpanzees was complicated by the ob-
servation that chimpanzees were mostly resistant to infection with
primary human HIV isolate that required the CCR5 chemokine receptor
for cell entry. This discovery brought pause to the vaccine field, since
none of the vaccines in testing could elicit neutralizing antibodies against
the primary isolates that required CCR5 for infection. Later attempts to
block infection using a human monoclonal against a primary HIV-1 chal-
lenge were also less successful, though they showed some effect in re-
ducing acute phase viremia (Conley et al., 1996).
OCR for page 98
98 ASSESSING THE NECESSITY OF THE CHIMPANZEE
Notably, one chimpanzee did develop immunodeficiency after more
than a decade of subclinical infection with two prototype strains of
CXCR4-adapted HIV (Novembre et al., 1997). Isolation of a pathogenic
virus from this animal sparked a debate on the role of chimpanzees in
HIV vaccine research. Specifically, it was proposed that a pathogenic
virus could facilitate a direct test of vaccines designed to slow CD4+ T
cell loss and immunodeficiency, if not infection (Cohen, 1999; Letvin,
1998). Vaccinated chimpanzees were never challenged with this virus in
the face of persuasive ethical and scientific arguments (Cohen, 1999;
Prince and Andrus, 1998). From the scientific perspective, there was
considerable doubt about whether very rapid CD4+ T cell loss observed
after transmission of the virus to new animals was representative of hu-
man disease. Moreover, because immunodeficiency was not a consistent
finding, there were also practical concerns with design of a study involv-
ing two or three animals per group. These experimental infections with
the pathogenic HIV strain were perhaps the last conducted at a primate
research facility in the United States. No new HIV infection studies in
chimpanzees have been published in the past decade.
Studies on the origin of human HIV infection are beginning to yield
insight into a host-virus relationship so finely tuned that it cannot be re-
capitulated in an animal with 99 percent genetic identity. It is now appar-
ent that HIV originated from a chimpanzee simian immunodeficiency
virus (SIVcpz) introduced into human populations by zoonotic infection
at least three times since the beginning of the 20th century (Keele et al.,
2009a). Most simian retroviruses, including those from monkeys, are
restricted from growth in human cells by species-specific factors (see
section below on Monkey-human models of infection). SIVcpz is no ex-
ception, as Vpu and Nef proteins had to adapt to neutralize human
tetherin, a protein that is induced by interferon and restricts virus release
from infected cells (Lim et al., 2010; Sauter et al., 2009). Adaptations
like this one may explain attenuation of HIV infectivity for chimpanzees
and perhaps limit its value as a model for vaccine development.
The Hepatitis Viruses
Chimpanzees are currently used to study the host response to four
hepatitis viruses (HAV, HBV, HCV, and HEV) and to develop or refine
approaches for prevention and treatment of the liver disease that they
cause. Prevention and treatment of transmissible hepatitis in humans has
been a public health priority for over 60 years. Progress toward isolation
OCR for page 99
99
APPENDIX B
of the agent(s) responsible for the disease burden was slow, in part be-
cause hepatotropic viruses are fastidious and not easily propogated in cell
culture. By the 1960s there was strong clinical, epidemiological, and
immunological evidence for two distinct forms of transmissible hepatitis
in humans (Krugman and Giles, 1972). Type A (or infectious) hepatitis
had a short incubation period and was self-limited. Type B (or serum)
hepatitis had a longer incubation period and was characterized by the
prolonged presence of the Australia antigen (hepatitis B surface antigen;
HBsAg) in serum. Use of chimpanzees in hepatitis research predated the
discovery of the viruses that caused type A and B hepatitis. Sporadic
outbreaks of liver disease in chimpanzee colonies with occasional zoono-
tic transmission indicated that the animals might be susceptible to infec-
tion with human viruses (Maynard et al., 1972a). Transmission of type A
(Dienstag et al., 1975; Maynard et al., 1975) and B (Barker et al., 1973;
Maynard et al., 1972b) hepatitis to chimpanzees facilitated characteriza-
tion of both viruses and rapid development of diagnostics and highly ef-
fective vaccines. Chimpanzee research provided critical proof that HBV
infection was preventable by vaccination with HBsAg purified from the
serum of human carriers (Buynak et al., 1976a, 1976b; Purcell and Gerin,
1975), and for the transition to a safer recombinant subunit vaccine
(McAleer et al., 1984). Attenuated and inactivated vaccines were also
shown to prevent HAV infection of chimpanzees (Feinstone et al., 1983;
Provost et al., 1983; Purcell et al., 1992). The principle that a vaccine can
prevent disease when administered as post-exposure prophylaxis was
also established using HAV-infected chimpanzees (Purcell et al., 1992).
Universal childhood vaccination against HAV and HBV is now recom-
mended in the United States.
Chimpanzees were also critically important to the discovery of the
agent causing a third major form of human hepatitis. Studies published in
1975 concluded that unidentified type C hepatitis virus(es) were respon-
sible for post-transfusion hepatitis in subjects not infected with HAV or
HBV (Feinstone et al., 1975; Prince et al., 1974). The infectious nature
of non-A, non-B hepatitis was not established by experimental transmis-
sion of liver disease to uninfected humans, an approach used to define
features of type A and B hepatitis in the highly controversial
Willowbrook experiments (Krugman, 1986). Instead, evidence that the
disease was caused by a small, enveloped RNA virus was obtained by
physico-chemical analysis of patient serum that transmitted persistent
hepatitis to chimpanzees (Alter et al., 1978; Bradley et al., 1983, 1985;
Tabor et al., 1978). Serum that was titrated and serially passaged in
OCR for page 100
100 ASSESSING THE NECESSITY OF THE CHIMPANZEE
chimpanzees provided the pedigreed material from which the HCV ge-
nome was eventually cloned as described in 1989 (Choo et al., 1989).
All four hepatitis viruses remain significant public health problems
today. A box summarizing research objectives of contemporary hepatitis
virus research using chimpanzees is provided (Box 1). As described in
detail below, HAV, HBV, HCV, and HEV all cause robust infection in
chimpanzees. These viruses can cause the same spectrum of liver disease
observed in humans, although in both species most infections tend to
clinically mild and/or slowly progressive.
BOX 1
Major Uses of Chimpanzees in Infectious Disease Research
• Characterize and identify new infectious agents, especially those that
cannot be propagated in lower species or cell culture.
• Define mechanisms of protective innate and adaptive immunity and
pathogen evasion strategies. This is particularly important in settings
where early phases of acute infection are not easily identified in
humans, or infected tissues are not accessibly for studies of immunity.
• Establish that new concepts for vaccination or therapy of infection are
safe and effective before translation to humans.
• Determine if reagents critical to development of therapeutics like clonal
viruses or parasites replicate in a host closely related to humans.
Enteric Hepatitis Viruses
HAV and HEV cause acute hepatitis and self-limited infection in
humans and chimpanzees. Although liver disease may be somewhat
milder in chimpanzees, the kinetics and magnitude of virus replication,
onset of liver disease, and histopathological changes in the liver are simi-
lar to those in HAV-infected humans (Dienstag et al., 1975, 1976). The
course of HEV infection in chimpanzees is variable, ranging from low
viremia with no obvious liver disease to high viremia with biochemical
and histological evidence of hepatitis (Li et al., 2006; McCaustland et al.,
2000). This may be similar to the spectrum of disease in HEV-infected
humans (McCaustland et al., 2000). HAV and HEV infections are pre-
ventable by vaccination. The efficacy of a subunit HEV vaccine was ap-
OCR for page 101
101
APPENDIX B
proximately 90 percent in two large human trials in Nepal and China, but
there is uncertainty about the durability of protective immunity as cur-
rently formulated and how (or if) it will be deployed where needed
(Shrestha et al., 2007; Wedemeyer and Pischke, 2011; Zhu et al., 2010).
Thus it is likely that endemic and epidemic HEV will remain a cause of
serious liver disease in developing countries (Aggarwal, 2011). HEV
immunity and pathogenesis are still very poorly understood (Aggarwal,
2011). For HAV, socioeconomic development accompanied by improved
sanitation and opportunity for vaccination has changed epidemiology in
regions where the virus is still endemic, as illustrated by a recent out-
break in South Korea (Kim and Lee, 2010; Kwon, 2009). Under these
circumstances, HAV infection shifts from the first to the second and third
decades of life with an associated increase in the severity of disease. This
situation has highlighted a gap in knowledge about mechanisms of im-
munity and hepatocellular injury caused by HAV. Very recent studies in
chimpanzees provided insight into patterns of innate immunity and host
gene expression immediately after infection with HAV and HEV, with
the goal of understanding the pathogenesis of these infections and how
they compare to responses elicited by HCV that often establishes a per-
sistent infection (Lanford et al., 2011; Yu et al., 2010a). Follow up stud-
ies of adaptive immunity to these viruses in animals should be
anticipated. Similar studies in humans will be difficult, if not impossible,
because infections with these small RNA viruses are often not sympto-
matic for several weeks and access to liver may be challenging as there is
typically no medical need for liver biopsy.
HBV Worldwide, approximately 500 million people are infected with
HBV. Hepadnaviruses are widespread in nature and chimpanzees do har-
bor indigenous strains of HBV that can be distinguished from human
viruses based on genomic signatures despite overall identity of about 90
percent (Barker et al., 1975a, 1975b; Dienstag et al., 1976; Guidotti et
al., 1999; Hu et al., 2000; Rizzetto et al., 1981). Chimpanzees are never-
theless highly susceptible to challenge with human HBV. Chimpanzees
develop persistent and resolved infections after challenge with the virus
(Barker et al., 1975a, 1975b). The incubation period preceding symptoms
is long and biochemical evidence of acute hepatitis is associated with
parenchymal inflammation, as in man. The magnitude and general pat-
tern of viremia and antigenemia during the acute and chronic phases of
infection are also similar between the species (Barker et al., 1975a,
1975b; Kwon and Lok, 2011). Severe progressive hepatitis and cirrhosis
OCR for page 156
156 ASSESSING THE NECESSITY OF THE CHIMPANZEE
Parham, P., L. Abi-Rached, L. Matevosyan, A. K. Moesta, P. J. Norman,
A. M. Older Aguilar, and L. A. Guethlein. 2010. Primate-specific regulation
of natural killer cells. Journal Med Primatol 39:194-212.
Patel, V., A. Valentin, V. Kulkarni, M. Rosati, C. Bergamaschi, R. Jalah,
C. Alicea, J. T. Minang, M. T. Trivett, C. Ohlen, J. Zhao, M. Robert-Guroff,
A. S. Khan, R. Draghia-Akli, B. K. Felber, and G. N. Pavlakis. 2010. Long-
lasting humoral and cellular immune responses and mucosal dissemination
after intramuscular DNA immunization. Vaccine 28:4827-4836.
Patterson, L. J., N. Malkevitch, J. Pinczewski, D. Venzon, Y. Lou, B. Peng,
C. Munch, M. Leonard, E. Richardson, K. Aldrich, V. S. Kalyanaraman, G.
N. Pavlakis, and M. Robert-Guroff. 2003. Potent, persistent induction and
modulation of cellular immune responses in rhesus macaques primed with
Ad5hr-simian immunodeficiency virus (SIV) env/rev, gag, and/or nef
vaccines and boosted with SIV gp120. J Virol 77:8607-8620.
Penna, A., M. Pilli, A. Zerbini, A. Orlandini, S. Mezzadri, L. Sacchelli,
G. Missale, and C. Ferrari. 2007. Dysfunction and functional restoration of
HCV-specific CD8 responses in chronic hepatitis C virus infection.
Hepatology 45:588-601.
Permar, S. R., S. A. Klumpp, K. G. Mansfield, W. K. Kim, D. A. Gorgone,
M. A. Lifton, K. C. Williams, J. E. Schmitz, K. A. Reimann, M. K.
Axthelm, F. P. Polack, D. E. Griffin, and N. L. Letvin. 2003. Role of
CD8(+) lymphocytes in control and clearance of measles virus infection of
rhesus monkeys. J Virol 77:4396-4400.
Permar, S. R., S. A. Klumpp, K. G. Mansfield, A. A. Carville, D. A. Gorgone,
M. A. Lifton, J. E. Schmitz, K. A. Reimann, F. P. Polack, D. E. Griffin, and
N. L. Letvin. 2004. Limited contribution of humoral immunity to the
clearance of measles viremia in rhesus monkeys. J Infect Dis 190:998-1005.
Permar, S. R., S. S. Rao, Y. Sun, S. Bao, A. P. Buzby, H. H. Kang, and
N. L. Letvin. 2007. Clinical measles after measles virus challenge in simian
immunodeficiency virus-infected measles virus-vaccinated rhesus monkeys.
J Infect Dis 196:1784-1793.
Pitcher, C. J., S. I. Hagen, J. M. Walker, R. Lum, B. L. Mitchell, V. C. Maino,
M. K. Axthelm, and L. J. Picker. 2002. Development and homeostasis of T
cell memory in rhesus macaque. J Immunol 168:29-43.
Polacino, P., K. Larsen, L. Galmin, J. Suschak, Z. Kraft, L. Stamatatos,
D. Anderson, S. W. Barnett, R. Pal, K. Bost, A. H. Bandivdekar, C. J.
Miller, and S. L. Hu. 2008. Differential pathogenicity of SHIV infection in
pig-tailed and rhesus macaques. J Med Primatol 37(Suppl 2):13-23.
Poland, J. D., C. H. Calisher, T. P. Monath, W. G. Downs, and K. Murphy.
1981. Persistence of neutralizing antibody 30-35 years after immunization
with 17D yellow fever vaccine. B World Health Org 59:895-900.
Porter, D. W., F. M. Thompson, T. K. Berthoud, C. L. Hutchings, L. Andrews,
S. Biswas, I. Poulton, E. Prieur, S. Correa, R. Rowland, T. Lang,
J. Williams, S. C. Gilbert, R. E. Sinden, S. Todryk, and A. V. Hill. 2011. A
OCR for page 157
157
APPENDIX B
human Phase I/IIa malaria challenge trial of a polyprotein malaria vaccine.
Vaccine 29:7514-7522.
Price, D. A., A. D. Bitmansour, J. B. Edgar, J. M. Walker, M. K. Axthelm,
D. C. Douek, and L. J. Picker. 2008. Induction and evolution of
cytomegalovirus-specific CD4+ T cell clonotypes in rhesus macaques. J
Immunol 180:269-280.
Prince, A. M., and L. Andrus. 1998. AIDS vaccine trials in chimpanzees.
Science 282:2195-2196.
Prince, A. M., B. Brotman, G. F. Grady, W. J. Kuhns, C. Hazzi, R. W. Levine,
and S. J. Millian. 1974. Long-incubation post-transfusion hepatitis without
serological evidence of exposure to hepatitis-B virus. Lancet 2:241-246.
Prince, A. M., D. Pascual, L. B. Kosolapov, D. Kurokawa, L. Baker, and
P. Rubinstein. 1987. Prevalence, clinical significance, and strain specificity
of neutralizing antibody to the human immunodeficiency virus. J Infect Dis
156:268-272.
Prince, A. M., H. Reesink, D. Pascual, B. Horowitz, I. Hewlett, K. K. Murthy,
K. E. Cobb, and J. Eichberg. 1991. Prevention of HIV infection by passive
immunization with HIV immunoglobulin. AIDS Res Hum Retrov 7:971-
973.
Prince, A. M., B. Brotman, T. Huima, D. Pascual, M. Jaffery, and G. Inchauspe.
1992. Immunity in hepatitis C infection. J Infect Dis 165:438-443.
Provost, P. J., P. A. Conti, P. A. Giesa, F. S. Banker, E. B. Buynak, W. J.
McAleer, and M. R. Hilleman. 1983. Studies in chimpanzees of live,
attenuated hepatitis A vaccine candidates. Proc Soc Exp Biol Med 172:357-
363.
Pulendran, B., J. Miller, T. D. Querec, R. Akondy, N. Moseley, O. Laur,
J. Glidewell, N. Monson, T. Zhu, H. Zhu, S. Staprans, D. Lee, M. A. Brinton,
A. A. Perelygin, C. Vellozzi, P. Brachman, Jr., S. Lalor, D. Teuwen,
R. B. Eidex, M. Cetron, F. Priddy, C. del Rio, J. Altman, and R. Ahmed.
2008. Case of yellow fever vaccine–associated viscerotropic disease with
prolonged viremia, robust adaptive immune responses, and polymorphisms
in CCR5 and RANTES genes. J Infect Dis 198:500-507.
Purcell, R. H., and J. L. Gerin. 1975. Hepatitis B subunit vaccine: A preliminary
report of safety and efficacy tests in chimpanzees. Am J Med Sci 270:395-
399.
Purcell, R. H., E. D’Hondt, R. Bradbury, S. U. Emerson, S. Govindarajan, and
L. Binn. 1992. Inactivated hepatitis A vaccine: Active and passive
immunoprophylaxis in chimpanzees. Vaccine 10(Suppl 1):S148-S151.
Querec, T. D., R. S. Akondy, E. K. Lee, W. Cao, H. I. Nakaya, D. Teuwen,
A. Pirani, K. Gernert, J. Deng, B. Marzolf, K. Kennedy, H. Wu,
S. Bennouna, H. Oluoch, J. Miller, R.Z. Vencio, M. Mulligan, A. Aderem,
R. Ahmed, and B. Pulendran. 2009. Systems biology approach predicts
immunogenicity of the yellow fever vaccine in humans. Nat Immunol
10:116-125.
OCR for page 158
158 ASSESSING THE NECESSITY OF THE CHIMPANZEE
Raziorrouh, B., W. Schraut, T. Gerlach, D. Nowack, N. H. Gruner,
A. Ulsenheimer, R. Zachoval, M. Wachtler, M. Spannagl, J. Haas,
H. M. Diepolder, and M. C. Jung. 2010. The immunoregulatory role of
CD244 in chronic hepatitis B infection and its inhibitory potential on virus-
specific CD8+ T-cell function. Hepatology 52:1934-1947.
Reeves, R. K., J. Gillis, F. E. Wong, Y. Yu, M. Connole, and R. P. Johnson.
2010. CD16- natural killer cells: Enrichment in mucosal and secondary
lymphoid tissues and altered function during chronic SIV infection. Blood
115:4439-4446.
Reeves, R. K., P. A. Rajakumar, T. I. Evans, M. Connole, J. Gillis, F. E. Wong,
Y. V. Kuzmichev, A. Carville, and R. P. Johnson. 2011. Gut inflammation
and indoleamine deoxygenase inhibit IL-17 production and promote
cytotoxic potential in NKp44+ mucosal NK cells during SIV infection.
Blood 118:3321-3330.
Rehermann, B. 2009. Hepatitis C virus versus innate and adaptive immune
responses: A tale of coevolution and coexistence. J Clin Invest 119:1745-
1754.
Reimann, K. A., J. T. Li, R. Veazey, M. Halloran, I. W. Park, G. B. Karlsson,
J. Sodroski, and N. L. Letvin. 1996. A chimeric simian/human
immunodeficiency virus expressing a primary patient human
immunodeficiency virus type 1 isolate env causes an AIDS-like disease
after in vivo passage in rhesus monkeys. J Virol 70:6922-6928.
Rerks-Ngarm, S., P. Pitisuttithum, S. Nitayaphan, J. Kaewkungwal, J. Chiu,
R. Paris, N. Premsri, C. Namwat, M. de Souza, E. Adams, M. Benenson,
S. Gurunathan, J. Tartaglia, J. G. McNeil, D. P. Francis, D. Stablein,
D. L. Birx, S. Chunsuttiwat, C. Khamboonruang, P. Thongcharoen, M. L.
Robb, N. L. Michael, P. Kunasol, and J. H. Kim. 2009. Vaccination with
ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J
Med 361:2209-2220.
Rhee, E. G., and D. H. Barouch. 2009. Translational Mini-Review Series on
Vaccines for HIV: Harnessing innate immunity for HIV vaccine
development. Clin Exp Immunol 157:174-180.
Rijckborst, V., M. J. Sonneveld, and H. L. Janssen. 2011. Review article:
Chronic hepatitis B—anti-viral or immunomodulatory therapy? Aliment
Pharmacol Ther 33:501-513.
Rizzetto, M., M. G. Canese, R. H. Purcell, W. T. London, L. D. Sly, and
J. L. Gerin. 1981. Experimental HBV and delta infections of chimpanzees:
Occurrence and significance of intrahepatic immune complexes of HBcAg
and delta antigen. Hepatology 1:567-574.
Robinson, J. E., K. S. Cole, D. H. Elliott, H. Lam, A. M. Amedee, R. Means,
R. C. Desrosiers, J. Clements, R. C. Montelaro, and M. Murphey-Corb.
1998. Production and characterization of SIV envelope-specific rhesus
monoclonal antibodies from a macaque asymptomatically infected with a
live SIV vaccine. AIDS Res Hum Retrov 14:1253-1262.
OCR for page 159
159
APPENDIX B
Rosati, M., A. von Gegerfelt, P. Roth, C. Alicea, A. Valentin, M. Robert-Guroff,
D. Venzon, D. C. Montefiori, P. Markham, B. K. Felber, and G. N.
Pavlakis. 2005. DNA vaccines expressing different forms of simian
immunodeficiency virus antigens decrease viremia upon SIVmac251
challenge. J Virol 79:8480-8492.
Rudensey, L. M., J. T. Kimata, E. M. Long, B. Chackerian, and J. Overbaugh.
1998. Changes in the extracellular envelope glycoprotein of variants that
evolve during the course of simian immunodeficiency virus SIVMne
infection affect neutralizing antibody recognition, syncytium formation and
macrophage tropism, but not replication, cytopathicity or CCR-5 coreceptor
recognition. J Virol 72:209-217.
Sa, J. M., O. Twu, K. Hayton, S. Reyes, M. P. Fay, P. Ringwald, and
T. E. Wellems. 2009. Geographic patterns of Plasmodium falciparum drug
resistance distinguished by differential responses to amodiaquine and
chloroquine. P Natl Acad Sci USA 106:18883-18889.
Sabatini, M. J., P. Ebert, D. A. Lewis, P. Levitt, J. L. Cameron, and K. Mirnics.
2007. Amygdala gene expression correlates of social behavior in monkeys
experiencing maternal separation. J Neurosci 27:3295-3304.
Sambrook, J. G., A. Bashirova, H. Andersen, M. Piatak, G. S. Vernikos,
P. Coggill, J. D. Lifson, M. Carrington, and S. Beck. 2006. Identification of
the ancestral killer immunoglobulin-like receptor gene in primates. BMC
Genomics 7:209.
Sarma, S. V., U. T. Eden, M. L. Cheng, Z. M. Williams, R. Hu, E. Eskandar,
and E. N. Brown. 2010. Using point process models to compare neural
spiking activity in the subthalamic nucleus of Parkinson’s patients and a
healthy primate. IEEE T Bio-med Eng 57:1297-1305.
Sather, D. N., J. Armann, L. K. Ching, A. Mavrantoni, G. Sellhorn, Z. Caldwell,
X. Yu, B. Wood, S. Self, S. Kalams, and L. Stamatatos. 2009. Factors
associated with the development of cross-reactive neutralizing antibodies
during human immunodeficiency virus type 1 infection. J Virol 83:757-769.
Sauter, D., M. Schindler, A. Specht, W. N. Landford, J. Munch, K. A. Kim,
J. Votteler, U. Schubert, F. Bibollet-Ruche, B. F. Keele, J. Takehisa,
Y. Ogando, C. Ochsenbauer, J. C. Kappes, A. Ayouba, M. Peeters, G. H. Learn,
G. Shaw, P. M. Sharp, P. Bieniasz, B. H. Hahn, T. Hatziioannou, and
F. Kirchhoff. 2009. Tetherin-driven adaptation of Vpu and Nef function and
the evolution of pandemic and nonpandemic HIV-1 strains. Cell Host
Microbe 6:409-421.
Schatten, G., and S. Mitalipov. 2009. Developmental biology: Transgenic
primate offspring. Nature 459:515-516.
Schmitz, J. E., M. J. Kuroda, S. Santra, V. G. Sasseville, M. A. Simon, M. A.
Lifton, P. Racz, K. Tenner-Racz, M. Dalesandro, B. J. Scallon, J. Ghrayeb, M. A.
Forman, D. C. Montefiori, E. P. Rieber, N. L. Letvin, and K. A. Reimann.
1999. Control of viremia in simian immunodeficiency virus infection by
CD8+ lymphocytes. Science 283:857-860.
OCR for page 160
160 ASSESSING THE NECESSITY OF THE CHIMPANZEE
Schmitz, J. E., M. J. Kuroda, S. Santra, M. A. Simon, M. A. Lifton, W. Lin,
R. Khunkhun, M. Piatak, J. D. Lifson, G. Grosschupff, R. S. Gelman,
P. Racz, K. Tenner-Racz, K. A. Mansfield, N. L. Letvin, D. C. Montefiori,
and K. A. Reimann. 2003. Effect of humoral immune responses on
controlling viremia during primary infection of rhesus monkeys with simian
immunodeficiency virus. J Virol 77:2165-2173.
Schmokel, J., H. Li, E. Bailes, M. Schindler, G. Silvestri, B. H. Hahn, C.
Apetrei, and F. Kirchhoff. 2009. Conservation of Nef function across highly
diverse lineages of SIVsmm. Retrovirology 6:36.
Scinicariello, F., C. N. Engleman, L. Jayashankar, H. M. McClure, and
R. Attanasio. 2004. Rhesus macaque antibody molecules: Sequences and
heterogeneity of alpha and gamma constant regions. Immunology 111:66-
74.
Shiver, J. W., T. M. Fu, L. Chen, D. R. Casimiro, M. E. Davies, R. K. Evans, Z. Q.
Zhang, A. J. Simon, W. L. Trigona, S. A. Dubey, L. Huang, V. A. Harris, R.
S. Long, X. Liang, L. Handt, W. A. Schleif, L. Zhu, D. C. Freed, N. V.
Persaud, L. Guan, K. S. Punt, A. Tang, M. Chen, K. A. Wilson, K. B. Collins,
G. J. Heidecker, V. R. Fernandez, H. C. Perry, J. G. Joyce, K. M. Grimm, J.
C. Cook, P. M. Keller, D. S. Kresock, H. Mach, R. D. Troutman, L. A. Isopi,
D. M. Williams, Z. Xu, K. E. Bohannon, D. B. Volkin, D. C. Montefiori, A.
Miura, G. R. Krivulka, M. A. Lifton, M. J. Kuroda, J. E. Schmitz, N. L.
Letvin, M. J. Caulfield, A. J. Bett, R. Youil, D. C. Kaslow, and E. A. Emini.
2002. Replication-incompetent adenoviral vaccine vector elicits effective anti-
immunodeficiency-virus immunity. Nature 415:331-335.
Shoukry, N. H., A. Grakoui, M. Houghton, D. Y. Chien, J. Ghrayeb, K. A. Reimann,
and C. M. Walker. 2003. Memory CD8+ T cells are required for protection
from persistent hepatitis C virus infection. J Exp Med 197:1645-1655.
Shrestha, M. P., R. M. Scott, D. M. Joshi, M. P. Mammen, Jr., G. B. Thapa,
N. Thapa, K. S. Myint, M. Fourneau, R. A. Kuschner, S. K. Shrestha, M. P.
David, J. Seriwatana, D. W. Vaughn, A. Safary, T. P. Endy, and B. L. Innis.
2007. Safety and efficacy of a recombinant hepatitis E vaccine. N Engl J
Med 356:895-903.
Sidney, J., S. Asabe, B. Peters, K. A. Purton, J. Chung, T. J. Pencille, R. Purcell,
C. M. Walker, F. V. Chisari, and A. Sette. 2006. Detailed characterization
of the peptide binding specificity of five common Patr class I MHC
molecules. Immunogenetics 58:559-570.
Silvestri, G. 2009. Immunity in natural SIV infections. J Intern Med 265:97-109.
Smirnova, I., A. Poltorak, E. K. Chan, C. McBride, and B. Beutler. 2000.
Phylogenetic variation and polymorphism at the toll-like receptor 4 locus
(TLR4). Genome Biol 1:RESEARCH002.
Smit-McBride, Z., J. J. Mattapallil, M. McChesney, D. Ferrick, and S. Dandekar.
1998. Gastrointestinal T lymphocytes retain high potential for cytokine
responses but have severe CD4(+) T-cell depletion at all stages of simian
OCR for page 161
161
APPENDIX B
immunodeficiency virus infection compared to peripheral lymphocytes. J
Virol 72:6646-6656.
Smith, L. R., M. K. Wloch, M. Ye, L. R. Reyes, S. Boutsaboualoy, C. E. Dunne,
J. A. Chaplin, D. Rusalov, A. P. Rolland, C. L. Fisher, M. S. Al-Ibrahim,
M. L. Kabongo, R. Steigbigel, R. B. Belshe, E. R. Kitt, A. H. Chu, and R. B.
Moss. 2010. Phase 1 clinical trials of the safety and immunogenicity of
adjuvanted plasmid DNA vaccines encoding influenza A virus H5
hemagglutinin. Vaccine 28:2565-2572.
Smits, S. L., A. de Lang, J. M. van den Brand, L. M. Leijten, I. W. F. van,
M. J. Eijkemans, G. van Amerongen, T. Kuiken, A. C. Andeweg, A. D.
Osterhaus, and B. L. Haagmans. 2010. Exacerbated innate host response to
SARS-CoV in aged non-human primates. PLoS pathogens 6:e1000756.
Soderstrom, K., J. O’Malley, K. Steece-Collier, and J. H. Kordower. 2006.
Neural repair strategies for Parkinson’s disease: Insights from primate
models. Cell Transplant 15:251-265.
Sodora, D. L., C. J. Miller, and P. A. Marx. 1997. Vaginal transmission of SIV:
assessing infectivity and hormonal influences in macaques inoculated with
cell-free and cell-associated viral stocks. AIDS Res Hum Retrov 13:S1-S5.
Sodora, D. L., J. S. Allan, C. Apetrei, J. M. Brenchley, D. C. Douek, J. G. Else,
J. D. Estes, B. H. Hahn, V. M. Hirsch, A. Kaur, F. Kirchhoff, M. Muller-
Trutwin, I. Pandrea, J. E. Schmitz, and G. Silvestri. 2009. Toward an AIDS
vaccine: Lessons from natural simian immunodeficiency virus infections of
African nonhuman primate hosts. Nat Med 15:861-865.
St Gelais, C., and L. Wu. 2011. SAMHD1: A new insight into HIV-1 restriction
in myeloid cells. Retrovirology 8:55.
Stevens, H. E., J. F. Leckman, J. D. Coplan, and S. J. Suomi. 2009. Risk and
resilience: Early manipulation of macaque social experience and persistent
behavioral and neurophysiological outcomes. J Am Acad Child Ps 48:114-
127.
Sullivan, N. J., A. Sanchez, P. E. Rollin, Z. Y. Yang, and G. J. Nabel. 2000.
Development of a preventive vaccine for Ebola virus infection in primates.
Nature 408:605-609.
Sullivan, N. J., T. W. Geisbert, J. B. Geisbert, L. Xu, Z. Y. Yang, M. Roederer,
R. A. Koup, P. B. Jahrling, and G. J. Nabel. 2003. Accelerated vaccination
for Ebola virus haemorrhagic fever in non-human primates. Nature
424:681-684.
Sullivan, N. J., T. W. Geisbert, J. B. Geisbert, D. J. Shedlock, L. Xu,
L. Lamoreaux, J. H. Custers, P. M. Popernack, Z. Y. Yang, M. G. Pau,
M. Roederer, R. A. Koup, J. Goudsmit, P. B. Jahrling, and G. J. Nabel.
2006. Immune protection of nonhuman primates against Ebola virus with
single low-dose adenovirus vectors encoding modified GPs. PLoS Med
3:e177.
OCR for page 162
162 ASSESSING THE NECESSITY OF THE CHIMPANZEE
Sullivan, N. J., J. E. Martin, B. S. Graham, and G. J. Nabel. 2009. Correlates of
protective immunity for Ebola vaccines: Implications for regulatory
approval by the animal rule. Nature Rev Micro 7:393-400.
Tabor, E., R. J. Gerety, J. A. Drucker, L. B. Seeff, J.H. Hoofnagle, D. R.
Jackson, M. April, L. F. Barker, and G. Pineda-Tamondong. 1978.
Transmission of non-A, non-B hepatitis from man to chimpanzee. Lancet
1:463-466.
Tachibana, M., M. Sparman, H. Sritanaudomchai, H. Ma, L. Clepper,
J. Woodward, Y. Li, C. Ramsey, O. Kolotushkina, and S. Mitalipov. 2009.
Mitochondrial gene replacement in primate offspring and embryonic stem
cells. Nature 461:367-372.
Teng, M. N., S. S. Whitehead, A. Bermingham, M. St Claire, W. R. Elkins,
B. R. Murphy, and P. L. Collins. 2000. Recombinant respiratory syncytial
virus that does not express the NS1 or M2-2 protein is highly attenuated and
immunogenic in chimpanzees. J Virol 74:9317-9321.
Thimme, R., D. Oldach, K. M. Chang, C. Steiger, S. C. Ray, and F. V. Chisari.
2001. Determinants of viral clearance and persistence during acute hepatitis
C virus infection. J Exp Med 194:1395-1406.
Thimme, R., J. Bukh, H. C. Spangenberg, S. Wieland, J. Pemberton, C. Steiger,
S. Govindarajan, R. H. Purcell, and F. V. Chisari. 2002. Viral and
immunological determinants of hepatitis C virus clearance, persistence, and
disease. P Natl Acad Sci USA 99:15661-15668.
Thimme, R., S. Wieland, C. Steiger, J. Ghrayeb, K. A. Reimann, R. H. Purcell,
and F. V. Chisari. 2003. CD8(+) T cells mediate viral clearance and disease
pathogenesis during acute hepatitis B virus infection. J Virol 77:68-76.
Ulmer, J. B., J. J. Donnelly, S. E. Parker, G. H. Rhodes, P. L. Felgner, V. J.
Dwarki, S. H. Gromkowski, R. R. Deck, C. M. EdWitt, A. Friedman, L. A.
Hawe, K. R. Leander, D. Mrtinex, H. C. Perry, J. W. Shiver, D. L.
Mongomery, and M. A. Liu. 1993. Heterologous protection against
influenza by injection of DNA encoding a viral protein. Science 259:1745-
1749.
Vaine, M., S. Wang, E. T. Crooks, P. Jiang, D. C. Montefiori, J. Binley, and
S. Lu. 2008. Improved induction of antibodies against key neutralizing
epitopes by human immunodeficiency virus type 1 gp120 DNA prime-
protein boost vaccination compared to gp120 protein-only vaccination. J
Virol 82:7369-7378.
van Montfort, T., M. Melchers, G. Isik, S. Menis, P. S. Huang, K. Matthews,
E. Michael, B. Berkhout, W. R. Schief, J. P. Moore, and R. W. Sanders.
2011. A chimeric HIV-1 envelope glycoprotein trimer with an embedded
granulocyte-macrophage colony-stimulating factor (GM-CSF) domain
induces enhanced antibody and T cell responses. J Biol Chem 286:22250-
22261.
Van Rompay, K. K. A. , and N. L. Haigwood. 2008. Pediatric AIDS: Maternal-
fetal and maternal-infant transmission of lentiviruses and effects on infant
OCR for page 163
163
APPENDIX B
development in nonhuman primates. In Primate Models of Children’s
Health and Developmental Disabilities. T. M. Burbacher, G. P. Sackett, and
K. S. Grant, editors. Amsterdam: Academic Press.
VandeBerg, J. L., S. M. Zola, J. J. Ely, and R. C. Kennedy. 2006. Monoclonal
antibody testing. J Med Primatol 35:405-406.
Vierboom, M., and B. ’t Hart. 2008. Spontaneous and experimentally induced
autoimmune diseases in nonhuman primates. In Primate Models of Children’s
Health and Developmental Disabilities. T. Burbacher, G. Sackett, and K.
Grant, editors. New York: Academic Press. Pp. 71-107.
Voytko, M. L., and G. P. Tinkler. 2004. Cognitive function and its neural
mechanisms in nonhuman primate models of aging, Alzheimer disease, and
menopause. Frontiers in Bioscience: A Journal and Virtual Library 9:1899-
1914.
Walker, C. M. 2010. Adaptive immunity to the hepatitis C virus. Adv Virus Res
78:43-86.
Walker, J. M., H. T. Maecker, V. C. Maino, and L. J. Picker. 2004. Multicolor
flow cytometric analysis in SIV-infected rhesus macaque. Meth Cell Bio
75:535-557.
Walker, L. M., M. D. Simek, F. Priddy, J. S. Gach, D. Wagner, M. B. Zwick,
S. K. Phogat, P. Poignard, and D. R. Burton. 2010. A limited number of
antibody specificities mediate broad and potent serum neutralization in
selected HIV-1 infected individuals. PLoS pathogens 6:e1001028.
Warfield, K. L., D. L. Swenson, G. G. Olinger, W. V. Kalina, M. J. Aman, and
S. Bavari. 2007a. Ebola virus-like particle-based vaccine protects
nonhuman primates against lethal Ebola virus challenge. J Infect Dis 196
(Suppl 2):S430-S437.
Warfield, K. L., D. L. Swenson, G. G. Olinger, W. V. Kalina, M. Viard,
M. Aitichou, X. Chi, S. Ibrahim, R. Blumenthal, Y. Raviv, S. Bavari, and
M. J. Aman. 2007b. Ebola virus inactivation with preservation of antigenic
and structural integrity by a photoinducible alkylating agent. J Infect Dis
196(Suppl 2):S276-S283.
Wedemeyer, H., and S. Pischke. 2011. Hepatitis: Hepatitis E vaccination—is
HEV 239 the breakthrough? Nat Rev Gastroenterol Hepatol 8:8-10.
Whitehead, S. S., M. G. Hill, C. Y. Firestone, M. St Claire, W. R. Elkins
B. R. Murphy, and P. L. Collins. 1999. Replacement of the F and G proteins
of respiratory syncytial virus (RSV) subgroup A with those of subgroup B
generates chimeric live attenuated RSV subgroup B vaccine candidates. J
Virol 73:9773-9780.
Willey, R. L., R. Byrum, M. Piatak, Y. B. Kim, M. W. Cho, J. L. Rossio Jr., J. Bess
Jr., T. Igarashi, Y. Endo, L. O. Arthur, J. D. Lifson, and M. A. Martin. 2003.
Control of viremia and prevention of simian-human immunodeficiency virus-
induced disease in rhesus macaques immunized with recombinant vaccinia
viruses plus inactivated simian immunodeficiency virus and human
immunodeficiency virus type 1 particles. J Virol 77:1163-1174.
OCR for page 164
164 ASSESSING THE NECESSITY OF THE CHIMPANZEE
Wilson, S. J., B. L. Webb, C. Maplanka, R. M. Newman, E. J. Verschoor, J. L.
Heeney, and G. J. Towers. 2008. Rhesus macaque TRIM5 alleles have
divergent antiretroviral specificities. J Virol 82:7243-7247.
Wooding, S., A. C. Stone, D. M. Dunn, S. Mummidi, L. B. Jorde, R. K. Weiss,
S. Ahuja, and M. J. Bamshad. 2005. Contrasting effects of natural selection
on human and chimpanzee CC chemokine receptor 5. Am J Hum Genet
76:291-301.
Wu, X., Z. Y. Yang, Y. Li, C. M. Hogerkorp, W. R. Schief, M. S. Seaman,
T. Zhou, S. D. Schmidt, L. Wu, L. Xu, N. S. Longo, K. McKee, S. O’Dell,
M. K. Louder, D. L. Wycuff, Y. Feng, M. Nason, N. Doria-Rose,
M. Connors, P. D. Kwong, M. Roederer, R. T. Wyatt, G. J. Nabel, and J. R.
Mascola. 2010. Rational design of envelope identifies broadly neutralizing
human monoclonal antibodies to HIV-1. Science 329:856-861.
Yant, L. J., T. C. Friedrich, R. C. Johnson, G. E. May, N. J. Maness, A. M. Enz, J. D.
Lifson, D. H. O’Connor, M. Carrington, and D. I. Watkins. 2006. The high-
frequency major histocompatibility complex class I allele Mamu-B*17 is
associated with control of simian immunodeficiency virus SIVmac239
replication. J Virol 80:5074-5077.
Yeh, W. W., P. Jaru-Ampornpan, D. Nevidomskyte, M. Asmal, S. S. Rao, A. P.
Buzby, D. C. Montefiori, B. T. Korber, and N. L. Letvin. 2009. Partial
protection of Simian immunodeficiency virus (SIV)-infected rhesus
monkeys against superinfection with a heterologous SIV isolate. J Virol
83:2686-2696.
Yin, J., A. Dai, J. Lecureux, T. Arango, M. A. Kutzler, J. Yan, M. G. Lewis,
A. Khan, N. Y. Sardesai, D. Montefiore, R. Ruprecht, D. B. Weiner, and J. D.
Boyer. 2010. High antibody and cellular responses induced to HIV-1 clade
C envelope following DNA vaccines delivered by electroporation. Vaccine
29:6763-6770.
Yu, C., D. Boon, S. L. McDonald, T. G. Myers, K. Tomioka, H. Nguyen, R. E.
Engle, S. Govindarajan, S. U. Emerson, and R. H. Purcell. 2010a.
Pathogenesis of hepatitis E virus and hepatitis C virus in chimpanzees:
Similarities and differences. J Virol 84:11264-11278.
Yu, C., D. Boon, S. L. McDonald, T. G. Myers, K. Tomioka, H. Nguyen, R. E.
Engle, S. Govindarajan, S. U. Emerson, and R. H. Purcell. 2010b.
Pathogenesis of hepatitis E virus and hepatitis C virus in chimpanzees:
Similarities and differences. J Virol 84:11264-11278.
Zhu, Y. D., J. Heath, J. Collins, T. Greene, L. Antipa, P. Rota, W. Bellini, and
M. McChesney. 1997. Experimental measles. II. Infection and immunity in
the rhesus macaque. Virology 233:85-92.
Zhu, F. C., J. Zhang, X. F. Zhang, C. Zhou, Z. Z. Wang, S. J. Huang, H. Wang,
C. L. Yang, H. M. Jiang, J. P. Cai, Y. J. Wang, X. Ai, Y. M. Hu, Q. Tang,
X. Yao, Q. Yan, Y. L. Xian, T. Wu, Y. M. Li, J. Miao, M. H. Ng, J. W.
Shih, and N. S. Xia. 2010. Efficacy and safety of a recombinant hepatitis E
OCR for page 165
165
APPENDIX B
vaccine in healthy adults: A large-scale, randomised, double-blind placebo-
controlled, phase 3 trial. Lancet 376:895-902.
Zolla-Pazner, S., X. P. Kong, X. Jiang, T. Cardozo, A. Nadas, S. Cohen,
M. Totrov, M. S. Seaman, S. Wang, and S. Lu. 2011. Cross-clade HIV-1
neutralizing antibodies induced with V3-scaffold protein immunogens
following priming with gp120 DNA. J Virol.
OCR for page 166
