Journal
JOURNAL OF IMMUNOLOGY
Volume 186, Issue 7, Pages 3882-3891Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1002799
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Funding
- U.S. Public Health Service [N01 50027, U54 AI081860]
- National Institute of Allergy and Infectious Diseases, National Institutes of Health [T32 AI007472, U54 AI057156]
- James D. McLaughlin
- Arizona Cancer Center [CCSG CA 023074]
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Older adults exhibit higher morbidity and mortality from infectious diseases compared with those of the general population. The introduction and rapid spread of West Nile virus (WNV) throughout the continental United States since 1999 has highlighted the challenge of protecting older adults against emerging pathogens: to this day there is no therapy or vaccine approved for human use against West Nile encephalitis. In this study, we describe the characterization of T and B cell responses in old mice after vaccination with RepliVAX WN, a novel West Nile encephalitis vaccine based on single-cycle flavivirus particles. In adult mice, RepliVAX WN induced robust and long-lasting CD4(+) and CD8(+) T cell and Ab (B cell) responses against natural WNV epitopes, similar to those elicited by primary WNV infection. Primary and memory T and B cell responses in old mice against RepliVAX WN vaccination were significantly lower than those seen in younger mice, similar to the response of old mice to infection with WNV. Surprisingly, both the quality and the quantity of the recall Ab and T cell responses in vaccinated old mice were improved to equal or exceed those in adult animals. Moreover, these responses together (but not individually) were sufficient to protect both old and adult mice from severe WNV disease upon challenge. Therefore, at least two cycles of in vivo restimulation are needed for selection and expansion of protective lymphocytes in older populations, and live, single-cycle virus vaccines that stimulate both cellular and humoral immunity can protect older individuals against severe viral disease. The Journal of Immunology, 2011, 186: 3882-3891.
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