Rapid SIV Env-specific mucosal and serum antibody induction augments cellular immunity in protecting immunized, elite-controller macaques against high dose heterologous SIV challenge

Three Indian rhesus macaques, Ad-SIV primed/protein boosted and exposed twice to high-dose mucosal SIV_mac251 challenges, exhibited elite control of viremia over 6.5years. They were negative for host factors associated with control of SIV infection. After a third intrarectal challenge with SIV_smE660, all controlled viremia, with one (macaque #5) maintaining undetectable viremia in blood. Acquisition was not blocked, but virus was contained in the jejunum and draining lymph nodes. Polyfunctional memory T cell responses and high-titered neutralizing and non-neutralizing serum and mucosal antibodies were present before and maintained post-challenge. The level of protection seen for animal #5 was predicted from analyses of gene transcription in jejunum 2weeks post-challenge. Macaques #7 and #9, exhibiting lower pre-challenge cellular and humoral immunity, partially controlled the SIV_smE660 challenge. Initial vaccine-induced control by macaque #5 extended to the SIV_smE660 challenge due to multiple immune mechanisms that were boosted and augmented by cryptic SIV exposure.