Multi-trial analysis of HIV-1 envelope gp41-reactive antibodies among global recipients of candidate HIV-1 vaccines

Abstract

Many participants in HIV-1 vaccine trials, who have not previously been exposed to or vaccinated against HIV-1, display serum immunoglobulin antibodies that bind the gp41 region of HIV-1 envelope prior to vaccination. Previous studies have hypothesized that these pre-existing antibodies may be cross-reactive and may skew future vaccine responses. In 12 large studies conducted by the HIV Vaccine Trial Network (HVTN) (n=1470 individuals), we find wide variation among participants in the pre-vaccine levels of gp41-reactive antibodies as measured by the binding antibody multiplex assay (BAMA). In the absence of exposure to the gp41 immunogen, anti-gp41 IgG levels were temporally stable over 26-52 weeks in repeated measures of placebo recipients. The analysis revealed that the geometric mean of pre-vaccine anti-gp41 IgG response was greater among participants in South Africa compared with participants in the United States. With gene-level metagenomic sequencing of pre-vaccination fecal samples collected from participants in one trial (HVTN 106), we detected positive associations between pre-vaccine anti-gp41 IgG and abundance of genes from multiple taxa in the Eubacteriales order. The genes most strongly associated with higher baseline anti-gp41 IgG mapped to a clade containing Blautia wexlerae and closely related strains. In trials with vaccine products containing the full or partial portion of gp41 immunogen alongside a gp120 immunogen, we did not find evidence that individuals with higher baseline anti-gp41 IgG had different levels of anti-gp120 IgG after vaccination compared to individuals with lower pre-vaccine anti-gp41 levels (pooled estimate of standardized mean difference -0.01 with a 95% CI [-0.37; 0.34]).

Evaluation of the accuracy of a multi-infection screening test based on a multiplex immunoassay targeting imported diseases common in migrant populations

“…The 10 antigens initially selected for the study are listed in Table 1. P24 (core antigen) and gp41 (envelope antigen) were selected for HIV serology, the first one for being indicative of acute infection 27 and the second one for being highly immunogenic during seroconversion 28 the 31-kDa recombinant antigen (NIE) antigen was selected for the serology of S.…”

Oral tolerance to systemic vaccination remains intact without RORγt expression in regulatory T cells

“… 2 , 3 Analysis of clinical trials of human immunodeficiency virus (HIV) vaccine candidates suggest a shared amino acid sequence between the envelope protein gp41 and proteins derived from Escherichia coli resident to the gastrointestinal (GI) tract. 2 , 4 , 5 , 6 , 7 Similarly, evidence suggests that the BCG vaccine used to prevent tuberculosis is less effective after exposure to environmental mycobacterium, suggesting diversion from building effective immunity against the pathogen due to pre-exposure of homologous antigens. 3 Here, we explore how pre-existing immunity in the gut could impact subsequent systemic vaccination.…”