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 143
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
Appendix A
Selection of Vaccine Candidates for Accelerated Development
JUDGING THE FEASIBILITY OF ACCELERATED VACCINE DEVELOPMENT
The selection of candidates for accelerated vaccine development depends in part on the mechanisms used to promote development. In the broadest sense, accelerated development could refer to any increase in emphasis or funding at any point along the continuum from disease definition and basic research through clinical trials to licensure.
In the early phases of vaccine development, the questions that need to be answered and the methods most appropriate for answering them may be difficult to define. Diverse approaches may be desirable until a scientific consensus emerges on the research directions most likely to be productive. Once the pathways for development have been set, however, the tasks needed to bring the vaccine to licensure are easier to identify and place in a uniform framework.
The National Institute of Allergy and Infectious Diseases’ (NIAID) influence to accelerate development is most likely to be effective in the latter stages of the continuum, probably through the contract mechanism. One of the committee’s first responsibilities was to identify vaccine candidates “ready” for this kind of support. Candidates were included in the ranking exercise described in Chapter 3 if committee members and knowledgeable consultants believed that their successful development was technically possible within 10 years. Candidates excluded from the analysis are described briefly in the supplement to this volume (see Appendix I), or in the committee’s first report (Appendix B, Institute of Medicine, 1985).
The knowledge required to determine the feasibility of accelerated development covers a wide spectrum, from characteristics of the pathogen to the composition of the target population. The latter is important not only for cost-effective vaccine delivery, but also to determine whether there is sufficient motivation to achieve reasonable utilization. No checklist can replace experienced judgment in assessing vaccine feasibility, but it is possible to identify certain factors that generally facilitate vaccine development (although all may not be essential):
OCR for page 144
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
knowledge of clinical signs and symptoms of the disease to allow differentiation from similar syndromes
identification of the pathogen and its major characteristics, including strains and serotypes, their infectivity, their virulence, their antigenicity, and the nature of essential immunogens
the existence of specific techniques for cultivation of the pathogen
identification of nonhuman models of infection
knowledge of the human immune response to the pathogen, including the duration and type of response (e.g., serum antibody, mucosal antibody, or cell-mediated immunity)
definition of the target population.
All aspects of the knowledge base that involve technical feasibility must be reassessed frequently: a vaccine not foreseeable today may become a reality in the future because of one unexpected development in the laboratory. Such developments are especially likely in the fields relevant to vaccine development because modern biotechnology has only begun to be explored.
ACCELERATED VACCINE DEVELOPMENT AND BASIC RESEARCH PRIORITIES
The criteria for selecting candidates for accelerated vaccine development do not address the general question of which vaccines are most needed in the developing world or its particular regions. For some diseases that impose major burdens, the knowledge base is insufficient to allow consideration of accelerated vaccine development by NIAID. Nevertheless, portions of the analysis described in this report can be applied to these disease problems to gain useful information about long-term goals and potential benefits. The description of disease burden considerations in Chapter 4 may be especially helpful in this regard.
The committee hopes that the selection of candidates for accelerated vaccine development will not divert funds from long-term basic research programs. For these programs, the scientific merit of the research proposal should continue to be the dominant criterion for funding.
SELECTING CANDIDATES FOR ACCELERATED DEVELOPMENT
The committee believed that its major contribution to establishing priorities would be the clear explication of a logical method for this task and that it probably could never satisfy all potential critics with its choice of candidates for assessment. As noted in Chapter 3, if a candidate is omitted from the full assessment, no conclusions should be made regarding its position in the priority rankings relative to the assessed contenders. When the prospects for vaccine control of disease were reasonable, however, the committee tried to include in the full analysis those candidates generally recognized in the developing world and the United States as major disease problems.
OCR for page 145
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
The process involved a number of iterations of selection, review, and revision. At an international workshop in Washington, D.C., on August 1–3, 1984, a draft list of infectious diseases prevalent in the developing world was reviewed and revised. This list was the starting point for candidate selection and is shown in Table A.1.
About 40 diseases were chosen from Table A.1 by the workshop participants as major health problems in the developing world. These diseases are listed in Table A.2. Some diseases were included in this list as models because vaccine prospects had been carefully reviewed in the committee’s prior assessment.
A working group at the workshop then assessed the state of knowledge on these diseases in three areas: disease mechanisms, protective mechanisms, and protective antigens. A simple scoring system was used (+/++/+++), and on the basis of scores, pathogen/disease entities were assigned to one of three categories: good prospects for the technical feasibility of vaccine development, promising prospects, or insufficient knowledge to evaluate prospects. Based on these judgments, candidates were either included in the full assessment, excluded from it, or subjected to further review by a committee subgroup which consulted with experts on relevant vaccine development efforts.
Appendixes D-1 through D-19 describe the prospects for immunizing against the candidate pathogens, and the supplement to this volume describes prospects and knowledge gaps for a range of diseases prevalent in the developing world and for which accelerated development efforts are not feasible or appropriate at this time.
For a number of the pathogens considered in the supplement, vaccine development prospects are such that their exclusion from consideration was a difficult decision. Because of rapid technologic advances in the vaccine development field, the state of knowledge and vaccine development prospects for these potential candidates should be regularly reviewed.
Table A.3 lists the pathogens for which the vaccine development prospects were reviewed in the committee’s first report. For various reasons, these pathogens were not included as primary contenders in the assessment of vaccine priorities for important diseases in the United States, although some are now included in this analysis.
REFERENCE
Institute of Medicine. 1985. New Vaccine Development: Establishing Priorities, Volume I. Diseases of Importance in the United States. Washington, D.C.: National Academy Press.
OCR for page 146
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
TABLE A.1 Important Diseases in Developing Countries
Amebiasis
E. histolytica
Ancylostomiasis (hookworm disease)
N. americanus
A. duodenale
A. ceylanicum
Ascariasis
A. lumbricoides
Brucellosis
B. abortus, biotypes 1–9
B. canis
B. melitensis, biotypes 1–3
B. suis, biotypes 1–4
Chlamydial infections (see also trachoma)
Chlamydia
Cholera
V. cholerae
Cryptosporidiosis
Cryptosporida spp.
Cytomegalovirus
Dengue fever
Immunological types 1–4
Group B togaviruses
Dengue hemorrhagic fever
Diarrheas, viral
Norwalk agent
Rotaviruses
Diarrheas, bacterial
Enteropathic E. coli
Enterotoxigenic E. coli
C. jejuni
Salmonella (nontyphoid)
Shigella
Herpes simplex virus
Herpesvirus varicellae
Japanese encephalitis
Leishmaniasis, cutaneous
Old world, L. tropica
New world, L. brasiliensis and L. mexicana
Leishmaniasis, visceral
L. donovani
Leprosy
M. leprae
Malaria
P. vivax
P. malariae
P. falciparum
P. ovale
Measles (rubeola)
Measles virus
Meningitis, aseptic
Enteroviruses (picornaviruses)
Coxsackie virus group A, types 2, 3, 7, 9
Coxsackie virus group B, types 2–5
Echovirus types 2, 5–7, 9–11, 14, 18, 30
Poliovirus
Arboviruses
Mumps
H. simplex and varicella viruses
Adenovirus
Meningitis, meningococcal
N. meningitidis
Mumps
Mumps virus, a myxovirus
Onchocerciasis (skin disease and river blindness), O. volvulus
Respiratory infections, acute bacterial
B. pertussis
S. pneumoniae
M. pneumoniae
H. influenzae
L. pneumophilia
Rift Valley fever
Rift Valley fever virus (group B togavirus)
Rubella
Rubella virus
Russian spring-summer encephalitis
Group B togavirus
Salmonellosis
S. typhimurium
S. heidelberq
S. newport
S. infantis
S. enteritidis
S. st. paul
Schistosomiasis
S. mansoni
S. haematobium
S. japonicum
S. intercalatum
Shigellosis
S. dysenteriae, group A
S. flexneri, group B
S. boydii, group C
S. sonnei, group D
Streptococcus group A
Streptococcus group B
Syphilis
T. pallidum
OCR for page 147
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
Diarrheas, parasitic
E. histolytica
G. lamblia
Diphtheria
C. diphtheriae
Dracunculiasis (Guinea worm disease)
Eastern equine encephalitis
Epstein-Barr virus
Filariasis
W. bancrofti
B. malayi
Giardiasis
G. lamblia
Gonorrhea
N. gonorrhoeae
Hantaan viruses and related agents
Hepatitis A
Hepatitis B
Hepatitis non-A, non-B
Paratyphoid fever
S. paratyphi A (S. enteritidis serotype paratyphoid A)
S. schottmuelleri (S. paratyphi B, S. enteritidis serotype paratyphoid B)
S. paratyphi C (S. hirschfeldii, S. enteritidis serotype paratyphoid C)
Plague
Y. pestis (P. pestis)
Poliomyelitis
Poliovirus types 1, 2, 3
Q fever
C. burneti (R. burneti)
Rabies
Rabiesvirus, a rhabdovirus
Relapsing fever
B. recurrentis
Respiratory infections, acute viral
Parainfluenza types 1–4
Respiratory syncytial virus
Adenovirus, types 1–7, 14, 21
Rhinoviruses
Coronaviruses
Types of coxsackie virus groups A and B
Echoviruses
Tetanus
C. tetani
Trachoma
C. trachomatis
Trichuriasis
T. trichiura (T. trichiurus)
Trypanosomiasis, African
T. gambiense
T. rhodensiense
Trypanosomiasis, South American
T. cruzi
Tuberculosis
M. tuberculosis
Typhoid
S. typhi
Typhus
Rickettsia
West Nile fever
West Nile fever virus (group B togavirus)
OCR for page 148
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries
TABLE A.2 Potential Candidate Diseases for New or Improved Vaccine Development
Amebiasis
Ancylostomiasis (hookworm)
Ascariasis
Brucellosis
Chlamydial infections
Cholera
Dengue fever
Diarrheas
E. coli
Norwalk agent
Salmonella (nontyphoid)
Shigella
Rotavirus
Campylobacter
Filariasis
Giardiasis
Gonorrhea
Hantaan virus
Hemophilus influenzae type B
invasive disease
Hepatitis A
Hepatitis B
Influenza virus
Japanese encephalitis
Leishmaniasis
Leprosy
Malaria
Measles
Meningococcal meningitis
Onchocerciasis
Skin disease
River blindness
Pertussis
Rabies
Respiratory infections
Parainfluenza
Respiratory syncytial virus
Adenovirus
Streptococcus pneumoniae
Hemophilus influenzae
Schistosomiasis
Streptococcus group A
Streptococcus group B
Trichuriasis
Trypanosomiasis
African
South American
Tuberculosis
Typhoid
Yellow fever
TABLE A.3 Pathogens Not Included as Candidates but Discussed in the Committee’s First Report (Appendix B)
Acquired immune deficiency syndrome agent
Adenovirus (respiratory disease)
Anaerobic bacteria
Clostridium botulinum
Clostridium difficile
Clostridium perfringens
Clostridium tetani
Chlamydia
Epstein-Barr virus
Giardia lamblia
Hospital acquired infections (gram-negative bacteria)
Nontypable Hemophilus influenzae
Non-A, non-B hepatitis
Histoplasma capsulatum
Human papilloma virus
Kawasaki disease agent
Legionella spp. (Legionnaire’s disease)
Mycoplasma pneumoniae
Rhinovirus
Rickettsia rickettsii (Rocky Mountain spotted fever)
Salmonella spp. (nontyphoidal)
Staphylococcus aureus
Streptococcus mutans
Treponema pallidum (syphilis)
Treponema-like spirochete of Lyme disease
Representative terms from entire chapter:
accelerated vaccine
