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The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1-uninfected RV144 vaccine recipients were reimmunized 6–8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 in the RV305 trial. Env-specific post-RV144 and RV305 boost memory B cell VH mutation frequencies increased from 2.9% post-RV144 to 6.7% post-RV305. The vaccine was well tolerated with no adverse events reports. While post-boost plasma did not have bnAb activity, the vaccine boosts expanded a pool of envelope CD4 binding site (bs)-reactive memory B cells with long third heavy chain complementarity determining regions (HCDR3) whose germline precursors and affinity matured B cell clonal lineage members neutralized the HIV-1 CRF01 AE tier 2 (difficult to neutralize) primary isolate, CNE8. Electron microscopy of two of these antibodies bound with near-native gp140 trimers showed that they recognized an open conformation of the Env trimer. Although late boosting of RV144 vaccinees expanded a novel pool of neutralizing B cell clonal lineages, we hypothesize that boosts with stably closed trimers would be necessary to elicit antibodies with greater breadth of tier 2 HIV-1 strains. Trial Registration: ClinicalTrials.gov NCT01435135

An abstract of the article "Integrated Systems Biology Analysis Reveals Contrasting Role for Innate Immune Response Genes in Conferring Risk of Infection in RV144 Trial" by Ali Filali-Mouhim, Slim Fourati, Francois Lefebvre, and colleagues is presented.

An abstract of the article "Evolutionary Analysis Identifies an MX2 Haplotype Associated with Natural Resistance to HIV-1 Infection" by Irma Saulle and colleagues is presented.

An abstract of the article "Sex Differences in Immune Variables in the RV144 Trial' by Darpun D. Sachdev, Hasan Ahmed, Yunda Huang, and colleagues is presented.

An abstract of the article "Induction of Antibodies with Long Variable Heavy Third Complementarity Determining Regions by Repetitive Boosting with AIDSVAX® B/E in RV144 Vaccinees" by Michael Anthony Moody, David Easterhoff, Thaddeus C. Gurley and colleagues is presented.

An abstract of the article "HIV-specific Antibody in Rectal Secretions Following Late Boosts in RV144 Participants (RV305)" by Siriwat Akapirat, Chitraporn Karnasuta, Sirinan Madnote and colleagues is presented.

Identifying whether viral features present in acute HIV-1 infection predetermine the development of neutralization breadth is critical to vaccine design. Incorporating such features in vaccine antigens could initiate cross-reactive antibody responses that could sufficiently protect vaccinees from HIV-1 infection despite the uniqueness of each founder virus. To understand the relationship between Env determinants and the development of neutralization breadth, we focused on 197 individuals enrolled in two cohorts in Thailand and East Africa (RV144 and RV217) and followed since their diagnosis in acute or early HIV-1 infection. We analyzed the distribution of variable loop lengths and glycans, as well as the predicted density of the glycan shield, and compared these envelope features to the neutralization breadth data obtained 3 years after infection (n =121). Our study revealed limited evidence for glycan shield features that associate with the development of neutralization breadth. While the glycan shield tended to be denser in participants who subsequently developed breadth, no significant relationship was found between the size of glycan holes and the development of neutralization breadth. The parallel analysis of 3,000 independent Env sequences showed no evidence of directional evolution of glycan shield features since the beginning of the epidemic. Together, our results highlight that glycan shield features in acute and early HIV-1 infection may not play a role determinant enough to dictate the development of neutralization breadth and instead suggest that the glycan shield's reactive properties that are associated with immune evasion may have a greater impact. [ABSTRACT FROM AUTHOR]

The Thai HIV phase III prime/boost vaccine trial (RV144) using ALVAC-HIV (vCP1521) and AIDSVAX B/E was, to our knowledge, the first to demonstrate acquisition efficacy. Vaccine-induced, cell-mediated immune responses were assessed. T cell epitope mapping studies using IFN-γ ELISPOT was performed on PBMCs from HIV-1-uninfected vaccine (w = 61) and placebo (n = 10) recipients using HIV-1 Env peptides. Positive responses were measured in 25 (41%) vaccinées and were predominantly CD4+ T cell-mediated. Responses were targeted within the HIV Env region, with 15 of 25 (60%) of vaccinées recognizing peptides derived from the V2 region of HIV-1 Env, which includes the 07 integrin binding site. Intracellular cytokine staining confirmed that Env responses predominated (19 of 30; 63% of vaccine recipients) and were mediated by polyfunctional effector memory CD4+ T cells, with the majority of responders producing both IL-2 and IFN-γ (12 of 19; 63%). HIV Env Ab titers were higher in subjects with IL-2 compared with those without IL-2-secreting HIV Env-specific effector memory T cells. Proliferation assays revealed that HIV Ag-speciflc T cells were CD4+, with the majority (80%) expressing CD107a. HTV-specific T cell lines obtained from vaccine recipients confirmed V2 specificity, polyfunctionality, and functional cytolytic capacity. Although the RV144 T cell responses were modest in frequency compared with humoral immune responses, the CD4+ T cell response was directed to HIV-1 Env and more particularly the V2 region [ABSTRACT FROM AUTHOR]

HIV/AIDS is a major public health problem worldwide, especially in developing countries. The development of a safe and effective HIV vaccine is central to stopping the epidemic and would be a great public health tool. The AIDS Vaccine for Asia Network (AVAN) is a group of concerned investigators committed to assisting regional and global HIV vaccine efforts. AVAN's focus on improving the coordination and harmonization of research, ethical reviews, clinical trial capacity, regulatory frameworks, vaccine manufacturing, community participation, and government advocacy could help accelerate HIV vaccine efforts in the region. At a meeting in November 2010, researchers from various countries in Asia presented their progress in HIV vaccine research and development. Six working groups discussed the current status, gaps and methods to strengthen capacity and infrastructure in various areas related to AIDS vaccine research and development. These discussions led to the development of prioritized action plans for the next 5 years. This report describes the gaps and challenges HIV vaccine research faces in the region and recommends improvement and standardization of facilities, and coordination and harmonization of all activities related to AIDS vaccine research and development, including possible technology transfer when a vaccine becomes available.

Acute bacterial meningitis is an important cause of morbidity and mortality in children. To estimate the incidence of meningitis caused by all types of bacteria in Thai children under five years of age, data were collected using a rapid assessment tool (RAT) and analyzed. Clinical and laboratory data from suspected meningitis cases for a one-year period were retrospectively collected from 5 selected catchment areas located in the 4 regions of the country. Adjusted incidences of confirmed bacterial meningitis were calculated based on laboratory quality and lumbar puncture rates. Seventy-five suspected meningitis cases were identified among 305,023 children under age five in the catchment areas, with an unadjusted incidence of 24.6 per 100,000. Of these, 66.2, 55.9, and 33.8% were unconfirmed bacterial, purulent, and confirmed bacterial meningitis cases, respectively. Among the confirmed bacterial meningitis cases, 39.1, 26.1, 21.7 and 13.0% were caused by Haemophilus influenzae type B, gram-positive cocci, gram-negative bacilli, and Neisseria meningitidis, respectively. After adjusting based on the RAT application, the incidence of confirmed bacterial meningitis was about double that of the unadjusted incidence. This study gives an interval of possible incidences of bacterial meningitis in children under age five, which is between the unadjusted (low estimate) and adjusted (high estimate) incidences.