Essential role for virus-neutralizing antibodies in sterilizing immunity against Friend retrovirus infection.
The current experiments use the Friend retrovirus model to demonstrate that vaccine-primed B cells are essential for sterilizing immunity, and the results indicate that the requisite function of these cells is the production of virus-neutralizing antibodies rather than priming or reactivation of T cells. B cell-deficient mice were poorly protected by vaccination, but adoptive transfer experiments showed that the T cells from B cell-deficient mice were primed as well as those from wild-type mice. Furthermore, passive transfer of virus-neutralizing antibodies completely compensated for B cell deficiency. The presence of virus-neutralizing antibodies at the time of infection was crucial for vaccine efficacy. Interestingly, virus-neutralizing antibodies worked synergistically with vaccine-primed T cells to provide a level of protection many orders of magnitude greater than either antibodies or immune T cells alone. Nonneutralizing antibodies also contributed to protection and acted cooperatively with neutralizing antibodies to reduce infection levels. These results emphasize the importance of inducing both T cell responses and virus-neutralizing antibody responses for effective retroviral vaccine protection.
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Ronald J
RJ
Messer
Ulf
U
Dittmer
Karin E
KE
Peterson
Kim J
KJ
Hasenkrug
D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D005622:Friend murine leukemia virus / Q000276:immunology* / Q000472:pathogenicity; D007942:Leukemia, Experimental / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D012192:Retroviridae Infections / Q000276:immunology / Q000517:prevention & control; D013601:T-Lymphocytes / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology / Q000517:prevention & control; D014765:Viral Vaccines / Q000494:pharmacology
D000914:Antibodies, Viral; D014765:Viral Vaccines