BackgroundThe efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity.MethodsHere, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders.ResultsFor both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes.ConclusionsThe data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.

Cytotoxic T lymphocyte (CTL) responses targeting specific HIV proteins, in particular Gag, have been associated with relative control of viral replication in vivo. However, Gag-specific CTL can also be detected in individuals who do not control the virus and it remains thus unclear how Gag-specific CTL may mediate the beneficial effects in some individuals but not in others. Here, we used a 10mer peptide set spanning HIV Gag-p24 to determine immunogen-specific T-cell responses and to assess functional properties including functional avidity and cross-reactivity in 25 HIV-1 controllers and 25 non-controllers without protective HLA class I alleles. Our data challenge the common belief that Gag-specific T cell responses dominate the virus-specific immunity exclusively in HIV-1 controllers as both groups mounted responses of comparable breadths and magnitudes against the p24 sequence. However, responses in controllers reacted to lower antigen concentrations and recognized more epitope variants than responses in non-controllers. These cross-sectional data, largely independent of particular HLA genetics and generated using direct ex-vivo samples thus identify T cell responses of high functional avidity and with broad variant reactivity as potential functional immune correlates of relative HIV control.

Kick&kill strategies combining drugs aiming to reactivate the viral reservoir with therapeutic vaccines to induce effective cytotoxic immune responses hold potential to achieve a functional cure for HIV-1 infection. Here, we report on an open-label, single-arm, phase I clinical trial, enrolling 15 early-treated HIV-1-infected individuals, testing the combination of the histone deacetylase inhibitor romidepsin as a latency-reversing agent and the MVA.HIVconsv vaccine. Romidepsin treatment resulted in increased histone acetylation, cell-associated HIV-1 RNA, and T-cell activation, which were associated with a marginally significant reduction of the viral reservoir. Vaccinations boosted robust and broad HIVconsv-specific T cells, which were strongly refocused toward conserved regions of the HIV-1 proteome. During a monitored ART interruption phase using plasma viral load over 2,000 copies/ml as a criterium for ART resumption, 23% of individuals showed sustained suppression of viremia up to 32 weeks without evidence for reseeding the viral reservoir. Results from this pilot study show that the combined kick&kill intervention was safe and suggest a role for this strategy in achieving an immune-driven durable viremic control.

ABSTRACT. Prior to 2007, efforts to monitor and conserve hawksbill turtles (Eretmochelys imbricata) in the eastern Pacific Ocean were opportunistic and records were virtually non-existent. The first abundance estimates were published in 2010, but contained limited data on the species. Ongoing research since that time has led to the identification of several rookeries, including sites containing large proportions of the overall hawksbill nesting currently known to occur in the region. Monitoring projects were established at several sites and have since provided substantial nesting data on the species. Here we summarize data collected between 1983 and March 2016 from all sites (n = 9) confirmed to host >10 nests in any given season to provide an update on hawksbill nesting in the eastern Pacific. We documented a total of 3,508 hawksbill nests, 265,024 hatchlings and 528 individual nesting females in the region. The vast majority of these records (99.4%, 99.9% and 99.6%, respectively) were generated subsequent to 2007, coinciding with the discovery of eight of the nine rookeries included in this study and the organization of monitoring efforts at those sites, which led to the increased documentation conferred here. Our findings should not be misconstrued as increases in actual nesting or signs of recovery, which could diminish the ongoing need for conservation actions, but rather as optimism, that there is still an opportunity to restore the species in the eastern Pacific. The top three sites in terms of average annual number of nests were Estero Padre Ramos (Nicaragua; 213.2 ± 47.6 nests), Bahia de Jiquilisco (El Salvador; 168.5 ± 46.7 nests) and Aserradores (Nicaragua; 100.0 ± 24.0 nests), and all three sites are located in mangrove estuaries in Central America, highlighting the importance of these rookeries/habitats for the survival and recovery of hawksbills in the region. The remaining six sites received between 6.9 ± 7.3 nests (Costa Careyes, Mexico) and 59.3 ± 17.7 nests (Los Cobanos, El Salvador) annually. By integrating data collected on nesting hawksbills with local conservation realities at the most important known hawksbill rookeries in the eastern 572 2 Latin American Journal of Aquatic Research Pacific, we provide a more holistic view of the conservation status and management needs of the species in this ocean region.