Abstract
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 dN/dS ratios in viruses sampled from each individual using three different methods. ANOVA analyses detected significant differences in dN/dS ratios among races (P < 0.02). gp120 sequences from the black individuals showed higher mean dN/dS 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 dN/dS 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.
Highlights
More than 33 million people are currently infected with HIV-1, resulting in 2–3 million deaths every year
In 2003, the results were released for a phase III HIV-1 vaccine efficacy trial conducted in North America and The Netherlands (VAX004) [3]
This study tested the efficacy of bivalent vaccines containing recombinant HIV-1 envelope glycoprotein 120 antigens, the major antigen on the surface of the virus [4]
Summary
More than 33 million people are currently infected with HIV-1, resulting in 2–3 million deaths every year. To test whether levels of selection were significantly different between vaccinated and placebo individuals in different races, we analyzed 3 clones per individual from 345 infected North Americans from the VAX004 study (Table 1; data available at http://www.gsid.org). Significant differences (pairwise t-tests; P < 0.05) between black and white, Hispanic and "others" viral samples were observed for all the estimators before corrections, but only the comparisons involving SNAP and PAML estimates remained significant after the Benjamini and Hochberg's adjustment (Table 2). Blackplacebo patients showed significantly (lm coefficients; P < 0.02) higher mean dN/dS ratios (1.3, 1.38 and 1.66, for SNAP, PAML and HYPHY, respectively) than the other races (0.65–1.01, 0.84–1.14 and 0.73–1.56, respectively) These results might indicate that natural differences in the immune response may have increased viral rgp120 adaptation in blacks.
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