Journal
HUMAN VACCINES
Volume 4, Issue 3, Pages 246-250Publisher
LANDES BIOSCIENCE
DOI: 10.4161/hv.4.3.5318
Keywords
animal models; vaccines; immunogenicity; adjuvants; antigens
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Animal models are essential for acquiring safety, immunogenicity and efficacy data to support the development of novel vaccines. However, extrapolating such results to designing human trials is challenging due to species-specific differences in responses to antigens, adjuvants and pathogens. As well, most early vaccine work is conducted with in-bred mouse strains which may fail to uncover issues that could arise later in out-bred populations. Unlike drugs designed to be delivered systemically, vaccines work within a somewhat localized space, so allometric dose scaling to account for body size differences is not necessarily relevant. Comparison of immune responses and correlates of protection with a given antigen show widely variable results between animals and humans, even where protective immunity against challenge with the same pathogen can be studied. For adjuvants, it is possible to compare enhancement of immunogenicity compared to a non-adjuvant control vaccine. While some novel adjuvants provide similar levels of enhancement between species, others do not. It is also important to recognize the inter-relationship between antigens and adjuvants, since one can compensate for the other, masking particular effects. Despite all the limitations, animal immunogenicity and efficacy studies form an important part of pre-clinical development for novel vaccines, but considerable prudence is required when using and extrapolating results.
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