Protecting the Frontline in Biodefense Research The Special Immunizations Program (2011) / Chapter Skim
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5 New Vaccine Development and the Future Needs of the Special Immunizations Program
5 New Vaccine Development and the Future Needs of the Special Immunizations Program
Pages 95-114
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From page 95... ...
Vaccine development leading to a licensed product typically involves a series of steps, starting with initial research, development, and testing for im munogenicity and protective immunity in animal models. After those preclinical studies, investigators submit data to FDA to receive an Investigational New Drug (IND)
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From page 96... ...
And personnel working on the pilot and scale-up manufacturing of a potential vaccine candidate may benefit from SIP vaccination, particularly if at risk of exposure to large quantities of live pathogen strains. 5.2 NEW VACCINE DEVELOPMENT AND THE FUTURE NEEDS OF THE SPECIAL IMMUNIZATIONS PROGRAM Except for several licensed vaccines, the vaccines now used in the SIP are IND products and are no longer being manufactured (information on the available stocks of these vaccines is provided in Chapter 3)
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From page 97... ...
As time passes, and the existing stocks age, there is also increasing concern that degradation might result in changes that are not detected in the stability program but could adversely affect product quality or biological performance or lead to adverse reactions.1 The committee therefore believes that it may be prudent to have fresh materials prepared for some or all products and to have bridging clinical trials performed. Such a program could be rolled out in order of priority considering aspects such as the amount of available stocks, the likely size of the researcher user population, the age of the vaccine stocks, the vaccine product profile, and concerns about potency or other product-quality issues.
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From page 98... ...
Although fixed, hard-piped stainless-steel bioreactors and clean-in-place and sterilize-in-place facilities are still important for high-volume or dedicated product manufacture, the use of flexible, single-use equipment can reduce initial investment cost and support rapid manufacture of clinical supplies. For example, Bavarian Nordic manufactures a new investigational modified vaccinia Ankara smallpox vaccine in GE WAVE bioreactor bags.
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From page 99... ...
Moreover, the cell culture–based SIP vaccines would have been manufactured with fetal bovine serum in the medium used to expand cells before viral infection. As a result, from 2000 to 2003, the SIP repeated complete lot release testing and tracked down the sources of fetal bovine sera to document that the vaccines meet current requirements and to exclude the possibility of bovine spongiform encephalopathy contamination.
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From page 100... ...
without purification agents Inactivated wild-type Minimum BSL-2/3 No Not infectious; bacterial vaccines complexity; innate and adaptive (e.g., DTP, animal fermentation, cell immunity vaccines) culture, followed by inactivation, often without purification Inactivated wild-type Egg-adapted "Split" vaccines Egg-based wild-type No Not infectious; viral vaccines (e.g., current strains; processed to process -- complex; requires innate and adaptive animal vaccines, cell culture may remove core cell-culture BSL-3; immunity; "split" annual influenza use wild type components, process -- less attenuated, vaccines may have leaving surface complex egg-adapted, less severe injection antigens BSL-2/3 site reaction Replicating Recombinant Minimum May require Yes nonpathogenic heterologous complexity; lyophilization bacterial vectors antigens fermentation with (e.g., recombinant stabilizing commensal bacteria, agents oral typhoid, animal vaccines, experimental cancer vaccines)
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From page 101... ...
BSL-3 immunity Particulate vaccines Moderate to May require No Mimic whole-virus (virus-like particles, complex stabilants or vaccines in recruiting bacterial-cell ghosts, cross-linking; innate and adaptive self-assembled used in immunity subunit antigens) conjunction with adjuvants Purified proteins, Moderate to Minimal; No Generally poor peptides, complex many immunogens polysaccharides adsorbed to alum Conjugated Complex; two Minimal; No Improved immune proteins, peptides, fermentations, many response to purified polysaccharides isolations, adsorbed to antigens (e.g., pneumococcal, purifications; alum meningococcal, H
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From page 102... ...
TABLE 5.1 Continued 102 Transmissible Whole Bulk Process Formulation BSL to Immunologic Platforms Microorganisms Subunits Complexity Complexity Required Nonvaccinees Advantages DNA vaccines Typically Minimum Minimum No (?
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From page 103... ...
• Specific problems and issues with the existing vaccines (for example, substrate acceptability) , use of animal products in culture media or manufacturing steps (for example, use of fetal bovine serum or por cine trypsin)
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From page 104... ...
, new vaccine lots of selected existing investigational vaccines that have a reasonably straight forward manufacturing path and are not likely to be eclipsed by new technol ogy within that period could be made. That applies principally to inactivated vaccines against eastern equine encephalitis (EEE)
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From page 105... ...
The projected costs would be split between government and industry and two contracts have recently been announced for approximately $100 million each. However, the emphasis on production of civilian pandemic influenza vaccine limits the application of such a potential development and manufacturing facility for the SIP.
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From page 106... ...
Most of these systems also include technology for rendering the vaccine candidates safe (by gene deletions that prevent repli cation in vivo or the use of replicons that generate protein or subviral particles. Several vector platforms are essentially ready for use in generating new candidates that could be used in the SIP against existing and new target indi
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From page 107... ...
5.2.6 H5N1 Avian Influenza Vaccine H5N1 influenza virus can cause life-threatening human disease and may pose a risk to laboratory workers and the public in the event of an escape of the virus from laboratory containment (via an infected laboratory worker)
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From page 108... ...
. As can be seen in the table and the discussions above, numerous vaccine candidates of potential value to the SIP either are under development in the United States or abroad or are already licensed for use in other countries.
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From page 109... ...
Inactivated suckling hemorrhagic hemorrhagic fever mouse brain fever virus Japanese Japanese China, India, South Korea, SA14, tissue culture, encephalitis virus encephalitis Nepal, Sri Lanka (PATH 2007) modified live Kyasanur Forest Kyasanur Forest India Inactivated suckling disease virus disease mouse Hantaan virus Hemorrhagic South Korea, China Rat brain, tissue fever with renal culture, inactivated syndrome Junin virus Argentine Argentina Live, attenuated hemorrhagic fever Ebola Zaire virus Ebola Canada Vesicular stomatitis hemorrhagic fever virus replicating vector Severe acute SARS China Inactivated cell culture respiratory syndrome (SARS)
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From page 110... ...
EEE 3 Live, attenuated chimeric Sindbis/EEE WEE 3 Live, attenuated chimeric Sindbis/EEE VEE 3 Live, attenuated chimeric Sindbis/EEE Ebola/Marburg 4 Yes (deaths) Ad5 recombinant live vector VSV recombinant live vector VEE replicon fevera Rift Valley 4 Yes (deaths)
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From page 111... ...
Baxter No Preclinical or Phase I sanofi pasteur (Acambis) Yes Phase III Hawaii Biotech Yes Phase I monovalent vaccine in clinic)
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From page 112... ...
The investigational formalin-inactivated RVF vaccine developed in the United States was used to help protect laboratory workers in Egypt in the outbreak of 1977–1978 (J.M. Meegan, personal com munication)
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From page 113... ...
• Finding 11: Numerous vaccine candidates of potential value to the SIP either are under development in the United States or abroad or are already licensed for use in other countries (for example, Q-Vax, a Q fever vaccine developed in Australia)
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From page 114... ...
MCM effort. The committee also recognizes that manufacturing new stocks of existing SIP vaccines or incorporating some or all of the additional vaccines into the SIP must occur in the context of U.S.
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