Spike-specific IgG4 generated post BNT162b2 mRNA vaccination is inhibitory when directly competing with functional IgG subclasses.

COVID-19 vaccines proved vital in controlling the SARS-CoV-2 pandemic. Both neutralizing and effector-function activities of Spike-specific antibodies are important for their protective activity. Several studies have reported that COVID-19 mRNA vaccines can lead to elevated levels of Spike-specific immunoglobulin G4 (IgG4), an anti-inflammatory subclass with reduced binding to Fcγ receptors.

Geographical Differences in SARS-CoV-2 Antibody Response Dynamics and Neutralisation Profiles to Mild COVID-19: Lessons from a UK-Uganda Comparison.

: The global SARS-CoV-2 pandemic revealed stark variability in clinical outcomes across populations, underscoring the need for region-tailored vaccination strategies. To inform standardised global immunisation efforts, this study compared longitudinal binding antibody responses and neutralisation capacities in mild COVID-19 cases from Uganda and the United Kingdom (UK). : IgG responses to spike (S) and nucleocapsid (N) proteins, along with IgM responses to S and receptor-binding domain (RBD) proteins, were assessed in 29 Ugandan and 14 UK participants over 84 and 82 days, respectively.

Long-Term Immune Consequences of Initial SARS-CoV-2 A.23.1 Exposure: A Longitudinal Study of Antibody Responses and Cross-Neutralization in a Ugandan Cohort.

This study assessed the long-term dynamics of neutralizing antibodies in a Ugandan cohort primarily exposed to the A.23.1 SARS-CoV-2 variant, examining how this shaped immune breadth and potency against diverse strains following infection and prototype-based vaccination.

Broad and potent neutralizing antibodies are elicited in vaccinated individuals following Delta/BA.1 breakthrough infection.

With the emergence of SARS-CoV-2 viral variants, there has been an increase in infections in vaccinated individuals. Here, we isolated monoclonal antibodies (mAbs) from individuals experiencing a breakthrough infection (Delta or BA.1) to determine how exposure to a heterologous Spike broadens the neutralizing antibody response at the monoclonal level.

Endogenous antibody responses in REGN-COV2-treated SARS-CoV-2-infected individuals.

Neutralizing monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein have been developed for the treatment of COVID-19. Whilst antibody therapy has been shown to reduce the risk of COVID-19-associated hospitalization and death, there is limited understanding of the endogenous immunity to SARS-CoV-2 generated in mAb-treated patients and therefore ongoing susceptibility to future infections. Here we measure the endogenous antibody response in SARS-CoV-2-infected individuals treated with REGN-COV2 (Ronapreve).

Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer.

This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse.

The effect of Omicron breakthrough infection and extended BNT162b2 booster dosing on neutralization breadth against SARS-CoV-2 variants of concern.

COVID-19 vaccines are playing a vital role in controlling the COVID-19 pandemic. As SARS-CoV-2 variants encoding mutations in the surface glycoprotein, Spike, continue to emerge, there is increased need to identify immunogens and vaccination regimens that provide the broadest and most durable immune responses. We compared the magnitude and breadth of the neutralizing antibody response, as well as levels of Spike-reactive memory B cells, in individuals receiving a second dose of BNT162b2 at a short (3-4 week) or extended interval (8-12 weeks) and following a third vaccination approximately 6-8 months later.