Studies suggest that SARS-CoV-2 vaccination during pregnancy induces a divergence of maternal and infant umbilical cord antibody function

In a recent study posted on Bio Rxiv*Preprint server, investigators investigated differences in infant and maternal umbilical cord antibody function between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination during pregnancy.

*Important Notices: Bio Rxiv We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.

Background

Prenatal exposure to SARS-CoV-2 can affect neurodevelopment in infants, even in the absence of vertical transmission. However, the full extent of these effects is still unknown. Various studies in both humans and animals suggest that it is important to exploit different immune responses that can target different stages of viral infection and pathogenesis to achieve long-lasting protection. I’m here.

Immunoglobulin (Ig)-G antibodies are the primary mechanism of immune transfer to the fetus after messenger ribonucleic acid (mRNA) vaccination. Understanding the different IgG-mediated functions within the fetus will help develop strategies that harness maternal immunity to protect the infant.

About research

In the present study, researchers compared maternal and fetal cord blood samples from individuals who received the SARS-CoV-2 mRNA vaccine during pregnancy.

Maternal umbilical cord blood was collected from individuals who received an mRNA vaccine targeting the WA1 receptor binding domain (RBD) and/or who were infected with SARS-CoV-2 during pregnancy. Antibody function induced by vaccination was assessed by measuring neutralizing activity to prevent viral entry and infection.

In this study, we analyzed Fc effector functions triggered by SARS-CoV-2 infection and vaccination, specifically antibody-dependent natural killer cell activation (ADNKA), antibody-dependent cytotoxicity (ADCC), antibody-dependent complement deposition (ADCD), and antibody-dependent cellular phagocytosis (ADCP). In this study, SARS-CoV-2 RBD IgG, IgA, IgM, IgG1, IgG2, IgG3, and IgG4 were measured to identify vaccine-induced antibodies.

result

Almost 47 were vaccinated, 4 with mRNA-1273 and 43 with BNT162b2 vaccine. No significant difference was observed between the two groups. Those who were vaccinated during pregnancy were older on average than those who were only infected. I didn’t see it.

Almost 20% of those infected were asymptomatic, 40% had mild symptoms, 10% had moderate symptoms, 14% had severe symptoms and 16% had severe symptoms. Most vaccinees received her two doses of the vaccine, with the last dose given in the third trimester before delivery.

mRNA-vaccinated individuals showed higher cord-neutralizing activity against live SARS-CoV-2 (WA1/2020) than SARS-CoV-2-infected individuals. However, no significant changes were observed for SARS-CoV-2 Delta (B.1.617.2) and Omicron (BA.2) variants through focal reduction neutralization trials (FRNT). Vaccination during pregnancy increases cord-neutralizing activity over simple infection and provides better protection against future attacks from the same strain of virus.

In this study, vaccination during pregnancy was associated with RBD ADNKA (involving intracellular interferon (IFN)-g and tumor necrosis factor (TNF) alpha production and CD107a degranulation), ADCD, but not when compared with infection alone. , found that ADCP did not increase. After vaccination during pregnancy, levels of low-affinity activating FcgRIIa/CD32a and FcgRIIIa/CD16a, inhibitory FcgRIIb/CD32b, and high-affinity FcRN were elevated compared to infection. No statistical difference was observed between the infection-vaccine combination and the vaccine-only combination. Vaccination enhances the magnitude of some, but not all, umbilical RBD Fc receptor binding and Fc effector function.

Neutralizing activity was similar in paired maternal and umbilical cord samples regardless of immune exposure. Maternal levels of RBD Fc effector function were lower in ADNKA compared to cord blood. ADCP showed this observation, but RBD ADCD did not. Maternal blood showed lower relative binding to FcgRIIa/CD32a, FcgRIIb/CD32b, and FcgRIIIa/CD16a compared to cord blood, suggesting that low-affinity inhibitory and activating FcgRs inhibited ADNKA and ADCP. was consistent with regulation. No differences were seen in the high-affinity FcRNs involved in her IgG transport across the placenta.

An increase in RBD IgG1 was observed in umbilical cord samples, but no change in control influenza-specific IgG. Minimal detection of RBD IgA and IgM was observed. Maternal vaccination is associated with elevated levels of RBD IgG, especially her IgG1. RBD IgA and IgM levels showed an increase after vaccination, but no significant difference was observed. Vaccination during pregnancy increases levels of RBD IgG, especially her IgG1, in both maternal and fetal immune responses.

Partial overlap was observed in the coordination between Fc effectors and neutralizing functions in cord and maternal responses. In this study, we found that the association between RBD Fcg and ADNKA receptor binding and virus neutralization was similar between mothers and fetuses, regardless of exposure to immunity. A maternal sample showed a high prevalence of association with RBD ADCP after vaccination. Umbilical cord and maternal samples showed an association with her RBD ADCD after infection. Variation between umbilical cord and maternal samples was more pronounced after vaccination than after natural infection, indicating distinct responses associated with specific immune exposures.

Conclusion

The results of this study showed that two doses of a monovalent COVID-19 mRNA vaccine during pregnancy protected infants from COVID-19 complications and morbidity for up to 6 months after birth. However, the mechanisms behind this protection are not fully understood. Cord blood vaccination provides increased multifunctional breadth, overall scale and antibody potency against SARS-CoV-2 via viral RBD IgG, particularly IgG1, and differential antibody glycosylation.

*Important Notices: Bio Rxiv We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.