Ethnic differences in the adaptation rate of HIV gp120 from a vaccine trial

Differences in HIV-1 gp120 sequence variation were examined in North American volunteers who became infected during a phase III vaccine trial using the rgp120 vaccine. Molecular adaptation of the virus in vaccine and placebo recipients from different ethnic subgroups was compared by estimating the d(N)/d(S )ratios in viruses sampled from each individual using three different methods. ANOVA analyses detected significant differences in d(N)/d(S )ratios among races (P < 0.02). gp120 sequences from the black individuals showed higher mean d(N)/d(S )ratios for all estimators (1.24–1.45) than in other races (0.66–1.35), and several pairwise comparisons involving blacks remained significant (P < 0.05) after correction for multiple tests. In addition, black-placebo individuals showed significantly (P < 0.02) higher mean d(N)/d(S )ratios (1.3–1.66) than placebo individuals from the other races (0.65–1.56). These results suggest intrinsic differences among races in immune response and highlight the need for including multiple ethnicities in the design of future HIV-1 vaccine studies and trials

Longitudinal population analysis of dual infection with recombination in two strains of HIV type 1 subtype B in an individual from a phase 3 HIV vaccine efficacy trial

This study documents a case of coinfection (simultaneous infection of an individual with two or more strains) of two HIV-1 subtype B strains in an individual from a Phase 3 HIV-1 vaccine efficacy trial, conducted in North American and the Netherlands. We examined 86 full-length gp120 (env) gene sequences from this individual collected from nine different time points over a 20-month period. We estimated evolutionary relationships using maximum likelihood and Bayesian methods and inferred recombination breakpoints and recombinant sequences using phylogenetic and substitutional methods. These analyses identified two strongly supported monophyletic clades (clades A and B) of 14 and 69 sequences each and a small paraphyletic recombinant clade of three sequences. We then studied the genetic characteristics of these lineages by comparing estimates of genetic diversity generated by mutation and recombination and adaptive selection within a coalescent and maximum likelihood framework. Our results suggest significant differences on the evolutionary dynamics of these strains. We then discuss the implications of these results for vaccine development

Phylodynamics of HIV-1 from a Phase-III AIDS Vaccine Trial in North America

In 2003, a phase III placebo-controlled trial (VAX004) of a candidate HIV-1 vaccine (AIDSVAX B/B) was completed in 5,403 volunteers at high risk for HIV-1 infection from North America and the Netherlands. A total of 368 individuals became infected with HIV-1 during the trial. The envelope glycoprotein gene (gp120) from the HIV-1 subtype B viruses infecting 349 patients was sequenced from clinical samples taken as close as possible to the time of diagnosis, rendering a final data set of 1,047 sequences (1,032 from North America and 15 from the Netherlands). Here, we used these data in combination with other sequences available in public databases to assess HIV-1 variation as a function of vaccination treatment, geographic region, race, risk behavior, and viral load. Viral samples did not show any phylogenetic structure for any of these factors, but individuals with different viral loads showed significant differences (P = 0.009) in genetic diversity. The estimated time of emergence of HIV-1 subtype B was 1966–1970. Despite the fact that the number of AIDS cases has decreased in North America since the early 90s, HIV-1 genetic diversity seems to have remained almost constant over time. This study represents one of the largest molecular epidemiologic surveys of viruses responsible for new HIV-1 infections in North America and could help the selection of epidemiologically representative vaccine antigens to include in the next generation of candidate HIV-1 vaccines

International Perspectives on the Legal Environment for Selection

Perspectives from 22 countries on aspects of the legal environment for selection are presented in this article. Issues addressed include (a) whether there are racial/ethnic/religious subgroups viewed as "disadvantaged,” (b) whether research documents mean differences between groups on individual difference measures relevant to job performance, (c) whether there are laws prohibiting discrimination against specific groups, (d) the evidence required to make and refute a claim of discrimination, (e) the consequences of violation of the laws, (f) whether particular selection methods are limited or banned, (g) whether preferential treatment of members of disadvantaged groups is permitted, and (h) whether the practice of industrial and organizational psychology has been affected by the legal environmen

Phylodynamics of HIV-1 from a Phase III AIDS Vaccine Trial in Bangkok, Thailand

In 2003, a phase III placebo-controlled trial (VAX003) was completed in Bangkok, Thailand. Of the 2,546 individuals enrolled in the trial based on high risk for infection through injection drug use (IDU), we obtained clinical samples and HIV-1 sequence data (envelope glycoprotein gene gp120) from 215 individuals who became infected during the trial. Here, we used these data in combination with other publicly available gp120 sequences to perform a molecular surveillance and phylodynamic analysis of HIV-1 in Thailand.Phylogenetic and population genetic estimators were used to assess HIV-1 gp120 diversity as a function of vaccination treatment, viral load (VL) and CD4(+) counts, to identify transmission clusters and to investigate the timescale and demographics of HIV-1 in Thailand. Three HIV-1 subtypes were identified: CRF01_AE (85% of the infections), subtype B (13%) and CRF15_AE (2%). The Bangkok IDU cohort showed more gp120 diversity than other Asian IDU cohorts and similar diversity to that observed in sexually infected individuals. Moreover, significant differences (P<0.02) in genetic diversity were observed in CRF01_AE IDU with different VL and CD4(+) counts. No phylogenetic structure was detected regarding any of the epidemiological and clinical factors tested, although high proportions (35% to 50%) of early infections fell into clusters, which suggests that transmission chains associated with acute infection play a key role on HIV-1 spread among IDU. CRF01_AE was estimated to have emerged in Thailand in 1984.5 (1983-1986), 3-6 years before the first recognition of symptomatic patients (1989). The relative genetic diversity of the HIV-1 population has remained high despite decreasing prevalence rates since the mid 1990s.Our study and recent epidemiological reports indicate that HIV-1 is still a major threat in Thailand and suggest that HIV awareness and prevention needs to be strengthened to avoid AIDS resurgence

Innate immune cell activation after HIV-1 vaccine administration is associated with increased antibody production

The RV144 Thai phase III clinical trial’s canarypox–protein HIV vaccine regimen showed modest efficacy in reducing infection. We therefore sought to determine the effects of vaccine administration on innate cell activation and subsequent associations with vaccine-induced immune responses. RV306 was a randomized, double-blind clinical trial in HIV-uninfected Thai adults that tested delayed boosting following the RV144 regimen. PBMC collected from RV306 participants prior to and 3 days after the last boost were used to investigate innate immune cell activation. Our analysis showed an increase in CD38+ mucosal associated invariant T (MAIT) cells, CD38+ invariant natural killer T (iNKT) cells, CD38+ γδ T cells, CD38+, CD69+ and HLA-DR+ NK cells 3 days after vaccine administration. An increase in CD14-CD16+ non-classical monocytes and CD14+CD16+ intermediate monocytes accompanied by a decrease in CD14+CD16- classical monocytes was also associated with vaccine administration. Inclusion of ALVAC-HIV in the boost did not further increase MAIT, iNKT, γδ T, and NK cell activation or increase the proportion of non-classical monocytes. Additionally, NK cell activation 3 days after vaccination was positively associated with antibody titers of HIV Env-specific total IgG and IgG1. Vδ1 T cell activation 3 days after vaccine administration was associated with HIV Env-specific IgG3 titers. Finally, we observed trending associations between MAIT cell activation and Env-specific IgG3 titers and between NK cell activation and TH023 pseudovirus neutralization titers. Our study identifies a potential role for innate cells, specifically NK, MAIT, and γδ T cells, in promoting antibody responses following HIV-1 vaccine administration

Identity and diversity in Organizations.

Quaderni di Psicologia del Lavor