Developing a vaccine for HIV may be aided by a complete understanding of those rare cases where some HIV-infected individuals control replication of the virus1–3. The majority of these elite controllers (ECs) express HLA-B*57 or HLA-B*273. These alleles remain by far the most robust associations with low concentrations of plasma virus4,5, yet the mechanism of control in these individuals is not entirely clear. Here we vaccinated Indian rhesus macaques that express Mamu-B*08, an animal model for HLA-B*27-mediated elite control6, with three Mamu-B*08-restricted CD8+ T cell epitopes and demonstrate that these vaccinated animals controlled replication of the highly pathogenic SIVmac239 clonal virus. High frequencies of CD8+ T cells against these Vif and Nef epitopes in the blood, lymph nodes and colon, were associated with viral control. Moreover, the frequency of the Nef RL10-specific response correlated significantly with reduced acute phase viremia. Finally, two of the eight vaccinees lost control of viral replication in the chronic phase, concomitant with escape in all three targeted epitopes, further implicating these three CD8+ T cell responses in control of viral replication. Our findings indicate that narrowly targeted vaccine-induced virus-specific CD8+ T cell responses can control replication of the AIDS virus.

The precise immunological role played by CD4 ؉ T cells in retroviral infections is poorly defined. Here, we describe a new function of these cells, the elimination of retrovirus-infected macrophages. After experimental CD8 ؉ cell depletion, elite controlling macaques with set-point viral loads <500 viral RNA copies/mL mounted robust Gagand Nef-specific CD4 ؉ T cell responses during reestablishment of control with >54% of all virus-specific CD4 ؉ T cells targeting these 2 proteins. Ex vivo, these simian immunodeficiency virus (SIV)-specific CD4 ؉ T cells neither recognized nor suppressed viral replication in SIV-infected CD4 ؉ T cells. In contrast, they recognized SIV-infected macrophages as early as 2 h postinfection because of presentation of epitopes derived from virion-associated Gag and Nef proteins. Furthermore, virus-specific CD4 ؉ T cells displayed direct effector function and eliminated SIV-infected macrophages. These results suggest that retrovirus-specific CD4 ؉ T cells may contribute directly to elite control by inhibiting viral replication in macrophages.antigen processing and presentation ͉ HIV

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission.

Therapies to prevent maternal Zika virus (ZIKV) infection and its subsequent fetal developmental complications are urgently required. We isolated three potent ZIKV-neutralizing monoclonal antibodies (nmAbs) from the plasmablasts of a ZIKV-infected patient—SMZAb1, SMZAb2, and SMZAb5—directed against two different domains of the virus. We engineered these nmAbs with Fc LALA mutations that abrogate Fc-gamma receptor (FcγR) binding, thus eliminating potential therapy-mediated antibody-dependent enhancement (ADE). We administered a cocktail of these three nmAbs to nonhuman primates (NHP) one day before challenge with ZIKV and demonstrated that the nmAbs completely prevented viremia in serum following challenge. Given that numerous Abs have exceptional safety profiles in humans, the cocktail described here could be rapidly developed to protect uninfected pregnant women and their fetuses. Overline: Emerging infections

Here we describe a novel vaccine vector for expressing human immunodeficiency virus (HIV) antigens. We show that recombinant attenuated yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 Gag sequences can be used as a vector to generate SIV-specific CD8؉ T-cell responses in the rhesus macaque. Priming with recombinant BCG expressing SIV antigens increased the frequency of these SIVspecific CD8؉ T-cell responses after recombinant YF17D boosting. These recombinant YF17D-induced SIVspecific CD8؉ T cells secreted several cytokines, were largely effector memory T cells, and suppressed viral replication in CD4 ؉ T cells.