Association of a novel IgG3 allele with malaria in children from the Sepik region of Papua New Guinea.

Background: Susceptibility to malaria can be influenced by host genetic factors, including immune response genes. Antibodies against Plasmodium antigens are known to play an important role in protection from clinical disease. Polymorphisms in these antibodies may result in different functional properties that could provide protection from malaria.

Anti-spike IgG4 and Fc effector responses: The impact of SARS-CoV-2 vaccine platform-specific priming and immune imprinting.

Proportional increases in anti-Spike (S) IgG4 associated with decreased Fc effector functions have been reported following repeated mRNA, but not recombinant protein-based (rS) (NVX-CoV2373, Novavax, Inc.), SARS-CoV-2 vaccination. We demonstrate the first evidence of a negative correlation between anti-S IgG4 and neutralizing antibody (nAb), as well as antibody-dependent surrogate Fc effector functions.

Genetic markers of enhanced functional antibody responses to COVID-19 vaccination.

Introduction: Substantial population-level variation in vaccine-specific antibody responses has been observed following global coronavirus disease 2019 (COVID-19) vaccination efforts. Beyond the influence of clinical and demographic features, immunogenetic variation is suggested to underlie divergent serological responses following COVID-19 vaccination of distinct populations.

Methods: Immunoglobulin G1 (IgG1) allotypic markers (G1m) for 121 COVID-19 vaccinated healthy adults were genotyped via Sanger sequencing.

Afucosylated broadly neutralizing antibodies targeting the HIV envelope elicit enhanced NK-cell-mediated cytotoxicity against HIV-infected CD4+ T-cell and macrophage targets.

Enhancement of antibody-dependent cellular cytotoxicity is a promising adjunct approach to achieve HIV control in the absence of antiretroviral therapy but requires the development of potent antibody-dependent cellular cytotoxicity-eliciting antibodies that can recognize diverse HIV-infected cell types. A panel of broadly neutralizing antibodies targeting the HIV envelope was identified that specifically binds both HIV-infected CD4+ T cells and monocyte-derived macrophages. Afucosylated versions of these broadly neutralizing antibodies containing ≈30% less core fucose were generated and elicited a significant increase in antibody-dependent cellular cytotoxicity responses from natural killer cells against HIV-infected T-cell and monocyte-derived macrophage targets.

Systems serology analysis shows IgG1 and IgG3 memory responses six years after one dose of quadrivalent HPV vaccine.

The WHO has given a permissive recommendation for an off-label one-dose human papillomavirus (HPV) vaccine schedule to prevent cervical cancer, based on evidence of comparable protection to two or three doses of vaccine. While neutralizing antibodies are thought to be the primary mechanism of protection, the persistence of immunity and whether other antibody-mediated mechanisms of protection are involved is unclear. Using systems serology, we investigated HPV antibody responses in serum from Fijian girls who were unvaccinated or received one, two or three doses of quadrivalent HPV vaccine six years earlier.

Increased SARS-CoV-2 IgG4 has variable consequences dependent upon Fc function, Fc receptor polymorphism, and viral variant.

Repeated mRNA COVID-19 vaccination increases spike-specific immunoglobulin G4 (IgG4) titers. Here, we characterized the influence of increased IgG4 titers on a range of Fc-mediated responses. Elevated spike-specific IgG4 reduced binding to FcγRIIIa and decreased antibody-dependent cellular cytotoxicity.

Effect of Bacille Calmette-Guérin vaccination on immune responses to SARS-CoV-2 and COVID-19 vaccination.

Objectives: Bacille Calmette-Guérin (BCG) vaccination has off-target effects on disease risk for unrelated infections and immune responses to vaccines. This study aimed to determine the immunomodulatory effects of BCG vaccination on immune responses to vaccines against SARS-CoV-2.

Methods: Blood samples, from a subset of 275 SARS-CoV-2-naïve healthcare workers randomised to BCG vaccination (BCG group) or no BCG vaccination (Control group) in the BRACE trial, were collected before and 28 days after the primary course (two doses) of ChAdOx1-S (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) vaccination.

Randomized trial of same- versus opposite-arm coadministration of inactivated influenza and SARS-CoV-2 mRNA vaccines.

BACKGROUNDThe immunogenicity of current influenza vaccines needs improvement. Inactivated influenza and COVID-19 mRNA vaccines can be coadministered, but randomized controlled trial data are lacking on whether the 2 vaccines are more immunogenic if given in the same arm or opposite arms. Murine studies suggest mRNA vaccines can adjuvant influenza vaccines when coformulated and codelivered.

Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression.

HIV-1 infection leads to chronic disease requiring life-long treatment and therefore alternative therapeutics, a cure and/or a protective vaccine are needed. Antibody-mediated effector functions could have a role in the fight against HIV-1. However, the properties underlying the potential beneficial effects of antibodies during HIV-1 infection are poorly understood.

Mechanisms and implications of IgG4 responses to SARS-CoV-2 and other repeatedly administered vaccines.

Vaccine-induced immunoglobulin G (IgG) profiles can vary with respect to the predominant subclasses that characterize the response. Among IgG subclasses, IgG4 is reported to have anti-inflammatory properties, but can also exhibit reduced capacity for virus neutralization and activation of Fc-dependent effector functions. Here, we review evidence that IgG4 subclass responses can be disproportionately increased in response to some types of vaccines targeting an array of diseases, including pertussis, HIV, malaria, and COVID-19.

A systems serology approach to identifying key antibody correlates of protection from cerebral malaria in Malawian children.

Background: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins are expressed on the surface of infected erythrocytes, mediating parasite sequestration in the vasculature. PfEMP1 is a major target of protective antibodies, but the features of the antibody response are poorly defined.

Methods: In Malawian children with cerebral or uncomplicated malaria, we characterized the antibody response to 39 recombinant PfEMP1 Duffy binding like (DBL) domains or cysteine-rich interdomain regions (CIDRs) in detail, including measures of antibody classes, subclasses, and engagement with Fcγ receptors and complement.

Intravital Imaging of the Human Cornea Reveals the Differential Effects of Season on Innate and Adaptive Immune Cell Morphodynamics.

Purpose: Defining how the in vivo immune status of peripheral tissues is shaped by the external environment has remained a technical challenge. We recently developed Functional in vivo confocal microscopy (Fun-IVCM) for dynamic, longitudinal imaging of corneal immune cells in living humans. This study investigated the effect of seasonal-driven environmental factors on the morphodynamic features of human corneal immune cell subsets.

Antibody glycosylation correlates with disease progression in SIV- coinfected cynomolgus macaques.

Objectives: Tuberculosis (TB) remains a substantial cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) worldwide. However, the immunological mechanisms associated with the enhanced susceptibility among HIV-positive individuals remain largely unknown.

Methods: Here, we used a simian immunodeficiency virus (SIV)/TB-coinfection Mauritian cynomolgus macaque (MCM) model to examine humoral responses from the plasma of SIV-negative ( = 8) and SIV-positive ( = 7) MCM 8-week postinfection with ().

Mucosal antibody responses following Vaxzevria vaccination.

Mucosal antibodies play a key role in protection against breakthrough COVID-19 infections and emerging viral variants. Intramuscular adenovirus-based vaccination (Vaxzevria) only weakly induces nasal IgG and IgA responses, unless vaccinees have been previously infected. However, little is known about how Vaxzevria vaccination impacts the ability of mucosal antibodies to induce Fc responses, particularly against SARS-CoV-2 variants of concern (VoCs).