Chronic HIV-1 Infection Alters the Cellular Distribution of FcγRIIIa and the Functional Consequence of the FcγRIIIa-F158V Variant

Chronic HIV-infection modulates the expression of Fc gamma receptors (FcγRs) on immune cells and their antibody-dependent effector function capability. Given the increasingly recognized importance of antibody-dependent cellular cytotoxicity (ADCC) in HIV-specific immunity, we investigated the cellular distribution of FcγRIIIa on cytotoxic lymphocytes—natural killer cells and CD8+ T cells—and the effect of the FcγRIIIa-F158V variant on ADCC capacity in HIV-infected individuals (n = 23) and healthy controls (n = 23). Study participants were matched for F158V genotypes, carried two copies of the FCGR3A gene and were negative for FcγRIIb expression on NK cells. The distribution of CD56dimFcγRIIIabright and CD56negFcγRIIIabright NK cell subsets, but not FcγRIIIa surface expression, differed significantly between HIV-1 negative and HIV-1 positive donors. NK cell-mediated ADCC responses negatively correlated with the proportion of the immunoregulatory CD56brightFcγRIIIadim/neg cells and were lower in the HIV-1 positive group. Intriguingly, the FcγRIIIa-F158V variant differentially affected the NK-mediated ADCC responses for HIV-1 negative and HIV-1 positive donors. Healthy donors bearing at least one 158V allele had higher ADCC responses compared to those homozygous for the 158F allele (48.1 vs. 34.1%), whereas the opposite was observed for the HIV-infected group (26.4 vs. 34.6%), although not statistically significantly different. Furthermore, FcγRIIIa+CD8bright and FcγRIIIa+CD8dim T cell subsets were observed in both HIV-1 negative and HIV-1 positive donors, with median proportions that were significantly higher in HIV-1 positive donors compared to healthy controls (15.7 vs. 8.3%; P = 0.016 and 18.2 vs. 14.1%; P = 0.038, respectively). Using an HIV-1-specific GranToxiLux assay, we demonstrate that CD8+ T cells mediate ADCC through the delivery of granzyme B, which was overall lower compared to that of autologous NK cells. In conclusion, our findings demonstrate that in the presence of an HIV-1 infection, the cellular distribution of FcγRIIIa is altered and that the functional consequence of FcγRIIIa variant is affected. Importantly, it underscores the need to characterize FcγR expression, cellular distribution and functional consequences of FcγR genetic variants within a specific environment or disease state

A Candidate DNA Vaccine Encoding the Native SARS-CoV-2 Spike Protein Induces Anti-Subdomain 1 Antibodies

The ideal vaccine against viral infections should elicit antibody responses that protect against divergent strains. Designing broadly protective vaccines against SARS-CoV-2 and other divergent viruses requires insight into the specific targets of cross-protective antibodies on the viral surface protein(s). However, unlike therapeutic monoclonal antibodies, the B-cell epitopes of vaccine-induced polyclonal antibody responses remain poorly defined. Here we show that, through the combination of neutralizing antibody functional responses with B-cell epitope mapping, it is possible to identify unique antibody targets associated with neutralization breadth. The polyclonal antibody profiles of SARS-CoV-2 index-strain-vaccinated rabbits that demonstrated a low, intermediate, or high neutralization efficiency of different SARS-CoV-2 variants of concern (VOCs) were distinctly different. Animals with an intermediate and high cross-neutralization of VOCs targeted fewer antigenic sites on the spike protein and targeted one particular epitope, subdomain 1 (SD1), situated outside the receptor binding domain (RBD). Our results indicate that a targeted functional antibody response and an additional focus on non-RBD epitopes could be effective for broad protection against different SARS-CoV-2 variants. We anticipate that the approach taken in this study can be applied to other viral vaccines for identifying future epitopes that confer cross-neutralizing antibody responses, and that our findings will inform a rational vaccine design for SARS-CoV-2

MOESM2 of Perinatal HIV-1 transmission: Fc gamma receptor variability associates with maternal infectiousness and infant susceptibility

Additional file 2: Table S2. Association of the FcγRIIIb-HNA1a homozygous genotype with perinatal HIV-1 acquisition when compared to other combinations of FcγRIIIb-HNA allotypes. Univariate and multivariate analysis of associations of the FcγRIIIb-HNA1a homozygous genotype with perinatal HIV-1 acquisition when compared to other combinations of FcγRIIIb-HNA allotypes

Household transmission of the SARS-CoV-2 Omicron variant in Denmark

In late 2021, the Omicron SARS-CoV-2 variant overtook the previously dominant Delta variant, but the extent to which this transition was driven by immune evasion or a change in the inherent transmissibility is currently unclear. We estimate SARS-CoV-2 transmission within Danish households during December 2021. Among 26,675 households (8,568 with the Omicron VOC), we identified 14,140 secondary infections within a 1–7-day follow-up period. The secondary attack rate was 29% and 21% in households infected with Omicron and Delta, respectively. For Omicron, the odds of infection were 1.10 (95%-CI: 1.00-1.21) times higher for unvaccinated, 2.38 (95%-CI: 2.23-2.54) times higher for fully vaccinated and 3.20 (95%-CI: 2.67-3.83) times higher for booster-vaccinated contacts compared to Delta. We conclude that the transition from Delta to Omicron VOC was primarily driven by immune evasiveness and to a lesser extent an inherent increase in the basic transmissibility of the Omicron variant

Virus isolation and neutralisation of SARS-CoV-2 variants BA.2.86 and EG.5.1 [Correspondence]

International audienc