Background: We studied LAV protection in macaques, with and without depletion of B cells by anti-CD20 antibody, to assess the contribution of humoral immune responses to the protection afforded by the vaccine.

 

 

 Methods: Of 24 male, Mamu-A*01-, -B*17-, and -B*08- negative rhesus monkeys, 10 received multiple high dose anti-CD20 antibody injections (50 mg/kg; Rituxan, Genentech/ Biogen Idec Inc.) and SIVmac239Δnef vaccination followed by i.v. SIVmac239 challenge 100 days following vaccination. A second group of 10 animals received control antibody and SIVmac239Δnef vaccination followed by i.v. SIVmac239 challenge 100 days following vaccination. Four control animals were only challenged i.v. with pathogenic SIVmac239. Assays for T cell function, neutralizing antibody, and plasma viremia were performed.

 

 

 Results: Five of 10 anti-CD20 treated monkeys lacked SIV-specific antibodies on the day of SIVmac239 challenge. The other 5 showed anti-SIV responses, reflecting inadequate B cell depletion. All 10 control antibody-treated animals, and 4 of 5 animals with adequate B cell depletion showed no take of challenge virus. One B cell-depleted animal showed a very weak viremia. In contrast, all 4 non-vaccinated rhesus macaques developed typical SIVmac239 infection with high-level peak viremia at day 14 post challenge. Peak viremia in the one unprotected, B cell-depleted animal was delayed by 7 days (from day 14 to day 21). Challenge with SIVmac239 did not affect the number or frequency of effector and central memory CD4+ T cells in the vaccinated animals irrespective of B cell depletion. There was no significant difference in SIV-specific T cell responses in the 5 adequately depleted and 10 control antibody-treated vaccinated animals.

 

 

 Conclusions:

 These results suggest that B cell-mediated immune responses play a marginal role in the protection afforded by the live attenuated SIVmac239Δnef vaccine.