Bette Korber and Colleagues Study Waning Immunity Following COVID-19 Boosting

Bette Korber and Colleagues Study Waning Immunity Following COVID-19 Boosting

Bette Korber and Colleagues Study Waning Immunity Following COVID-19 Boosting

Bette Korber, a scientist at Los Alamos National Laboratory and the New Mexico Consortium, recently was part of a team that published Waning immunity and IgG4 responses following bivalent mRNA boosting in the February 2024 issue of Science Advances.

A recently used form of the COVID-19 vaccine was a bivalent mRNA booster which means it contains contain both the original Wuhan strain alongside the Omicron BA.1 or the Omicron BA.4/5 variant. When administered, this booster produces antibodies that target both the original “ancestral” Wuhan strain and the Omicron BA.1 or Omicron BA.4/5 SARS-CoV-2 variant to provide broader protection. At first these messenger RNA (mRNA) vaccines were highly effective against the first COVID-19 strain, but over time the bivalent mRNA booster has become less efficient against XBB variants. XBB variants are a potent mix of COVID-19 mutations that have made it easier to spread, including in people who have been vaccinated. The current COVID-19 vaccine is a XBB sub-lineage, XBB.1.5,  monovalent vaccine.

In this study, Korber and colleagues show the limited durability of neutralizing antibody (NAb) responses against XBB variants and isotype switching to immunoglobulin G4 (IgG4) responses following bivalent mRNA boosting. An NAb is an antibody that is responsible for defending cells from pathogens. They are produced naturally by the body as part of its immune response, and their production is triggered by both infections and vaccinations against infections.

What is isotype switching? It is a biological mechanism that changes a B cell’s production of antibody from one class to another; for example, from an isotype called IgM to an isotype called IgG. Isotope switching is important for the immune system’s ability to effectively combat a wide range of pathogens.

This study found that bivalent mRNA boosting elicited modest XBB.1- , XBB.1.5- , and XBB.1.16- specific NAbs that waned rapidly within 3 months. In contrast, bivalent mRNA boosting induced more robust and sustained NAbs against the ancestral WA1/2020 strain, suggesting immune imprinting. Following bi-valent mRNA boosting, serum antibody responses were primarily IgG2 and IgG4 responses with poor Fc functional activity. In contrast, a third monovalent mRNA immunization boosted all isotypes including IgG1 and IgG3 with robust Fc functional activity.

These data shows substantial immune imprinting for the ancestral spike and isotype switching to IgG4 responses following bivalent mRNA boosting, with important implications for future booster designs and boosting strategies.

For more information, see the entire article at: Waning immunity and IgG4 responses following bivalent mRNA boosting