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  5. Vaccine outcomes to SARS-CoV-2 vaccine and variant viruses among pregnant people by Sabra Klein - 03/19/2024
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Webcast | Virtual

Event Title
Vaccine outcomes to SARS-CoV-2 vaccine and variant viruses among pregnant people by Sabra Klein
March 19, 2024

Date:
March 19, 2024

Johns Hopkins University (JHU) CERSI

Tuesday, March 19th, 2024
3:00 – 4:00 PM (Eastern Standard Time)

Presented By

Sabra Klein, PhD

Sabra Klein, PhD
Professor of Molecular Microbiology and Immunology
Johns Hopkins Bloomberg School of Public Health

About the Presentation

Pregnant people are at risk for more severe outcomes from many infectious diseases, including COVID-19. Pregnant patients, however, were not included in initial clinical trials of EUA SARS-CoV-2 vaccines and current rates of vaccine uptake among pregnant people remain less than <15%. Through our CERSI funding, we aimed to define the serological (i.e., neutralizing and non-neutralizing antibody functions), cellular, and immunometabolic immune responses to COVID-19 mRNA vaccines in pregnant compared with non-pregnant people, with qualitative assessment of pregnant people expressing hesitancy about COVID-19 vaccines. During the 2022-2023 vaccination campaign, plasma and peripheral blood mononuclear cells were obtained prior to and one month after receipt of the bivalent mRNA booster vaccines from pregnant and non-pregnant patients. Baseline and 28-day post vaccination samples were used to assess antigen-specific immunoglobulin isotype responses and live virus neutralizing antibody (nAb) responses, in addition to the crystallizable fragment (Fc) receptor affinity. For isotyping, IgM, IgG (IgG1-4), and IgA (IgA1-2) binding to antigen (i.e., 2022-2023 COVID-19 vaccine ancestral spike and nucleocapsid protein, BA.5, XBB.1, and JN.1 spike proteins) were multiplexed using a Luminex Intelliflex. Similarly, we assayed the ability of antigen specific antibodies to bind the following Fc receptors (FcRs): FcγRIIA-R, FcγRIIA-H, FcγRIIb, FcγRIIIA-V, FcγRIIIA-F, FcγRIIIB, FcRn, and FcαR. For each assay, the mean fluorescence intensity (MFI) of secondary antibody-conjugated to Phycoerythrin (PE), or FcR protein-conjugated to PE for each bead region was measured to quantify antigen-specific immunoglobulin isotypes and FcR responses in each sample at 0- and 28-days post vaccination. To date, we have observed that pregnant people mount sufficient antibody responses to ancestral spike, but not spike proteins from omicron variants of concern (VOC). In response to the omicron BA.5, XBB1.5, and JN.1 spike proteins, antibodies from pregnant patients are less cross-reactive than are antibodies from non-pregnant patients, which is most pronounced for IgG1-4 as well as diverse FcRs. FcγRIIIA is primarily found on NK cells and may reflect antibody-dependent cytolytic activity (ADCC). FcγRIIA, the only IgG receptor on platelets, binding was greater in non-pregnant than pregnant patients. In vaccine responses, FcγRIIA stimulates platelet aggregation and has been linked with abnormal autoantibody production and adverse vaccine reactions, which we show are more common in nonpregnant females. In response to vaccination, IgG4 has been implicated as inducing a more anti-inflammatory immune response, with a decrease in Fc receptor activity as measured by antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent complement deposition (ADCD), and may help explain how pregnancy impacts FcR affinity. Finally, antibodies binding to FcRn were elevated after vaccination in nonpregnant, but not pregnant, patients in response to VOC. Because vaccine-induced antibody binding to FcRn has been implicated in cellular memory responses and sustained protection, reduced responses during pregnancy could suggest reduced long-term protection afforded by COVID-19 vaccines against novel variants. Analyses of samples from pregnant and non-pregnant patients are ongoing for measures of cellular and metabolic responses as well as associations with changes in sex steroid hormone concentrations during pregnancy.

Acknowledgements: This presentation is supported by the US Food and Drug Administration (FDA) of the US Department of Health and Human Services (HHS) as part of a financial assistance award (U01FD005942). The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.

About the Presenter

Dr. Klein is a Professor of Molecular Microbiology & Immunology, Biochemistry & Molecular Biology, and International Health at the Johns Hopkins Bloomberg School of Public Health and Department of Medicine at the Johns Hopkins School of Medicine. She co-directs the Johns Hopkins Center for Women’s Health, Sex, and Gender Research. She is an expert on sex differences in immune responses to microbes and vaccines, with interrogation of sex-specific effects of aging and pregnancy in humans and animal models. She has over 200 peer-reviewed publications, authored several book chapters, edited three books on the broad topics of sex differences in response to infection and treatments for infectious diseases, and is listed in the top 2% researchers worldwide for publications. During the 2009 influenza pandemic, she was commissioned by the WHO to evaluate and publish a report on the impact of sex, gender, and pregnancy on the outcome of influenza virus infection. During the COVID-19 pandemic, Dr. Klein wrote commentaries for several journals and was interviewed by several major news media outlets about sex differences in immunity, disease outcomes, and responses to vaccines. She is a fellow of the American Academy of Microbiology and the American Association for the Advancement of Science. In 2023, she received the Vivian Pinn Award for Outstanding Research in Women’s Health.

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