In a recent study posted to the medRxiv* preprint server, researchers evaluated the immune responses to coronavirus disease 2019 (COVID-19) primary vaccinations and booster doses during pregnancy and the impact of the maternal booster dose on transplacental antibody transfer to the infant in the United States (US).
Pregnant women are at a greater risk of COVID-19 severity and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected infants aged less than six months are at a greater risk of hospital admission. Therefore, SARS-CoV-2 vaccinations are essential during pregnancy for COVID-19 mitigation. Beginning in October 2021, gestational women gained eligibility for COVID-19 vaccine boosters, yet data on the booster-induced immune responses during pregnancy is still limited.
About the study
In the present study, researchers measured the immune responses induced by COVID-19 primary and booster messenger ribonucleic acid (mRNA) vaccinations during pregnancy and transplacental antibody transfer to the infant in the US.
The study comprised pregnant women enrolled between 6 July 2021 and 31 January 2022, from nine academic locations, with follow-ups up to one-year post-delivery. The study participants were vaccinated with two primary doses of the mRNA-1273 vaccine or Pfizer-BioNTech vaccines and/or booster vaccination of either of the COVID-19 mRNA vaccines during pregnancy and childbirth.
Serum samples were obtained before and after COVID-19 mRNA vaccination (after two weeks of vaccination until delivery of their newborns). Maternal and cord blood samples were obtained during delivery. The binding antibodies or immunoglobulin G (IgG) titers to SARS-CoV-2 spike (S) protein and the S receptor-binding domain (RBD) were evaluated and denoted by binding antibody units (BAU)/mL.
The neutralizing antibody (nAb) titers were determined using live virus focus reduction neutralization titer (FRNT) assays with viruses bearing mutant S of the SARS-CoV-2 Delta, D614G, and Omicron BA.1 strains. The nAb titers were expressed as the serum inhibitory dilution needed to neutralize SARS-CoV-2 strains by 50% (ID50). The transplacental transfer of antibodies was evaluated based on the ratios of antibody titers in the sera obtained from maternal blood and cord blood during delivery.
The study exposure was primary or booster COVID-19 mRNA vaccination during pregnancy and the prime outcome was the generation of SARS-CoV-2 binding IgG titers and nAb titers after primary or booster vaccinations during pregnancy and antibody transfer to the infants. Immune responses were compared between primary and booster vaccinees in maternal sera at delivery and in cord blood.
A total of 240 mothers were included in the analysis, of which, 100 women and 67 women received the two-dose primary vaccination regimens of Pfizer-BioNTech vaccines (102 infants) and mRNA-1273 vaccines (68 infants), respectively. Booster vaccinations were administered to 73 women (75 infants), of which, most (81%) were homologous vaccine boosters.
Serological binding S and S RBD IgG titers were observed among all primary and booster vaccinees during the follow-up assessments (after vaccination and at delivery) and among all samples of cord blood. Substantially greater titers were detected during the follow-ups among booster vaccinees than the primary mRNA vaccinees. At delivery, S IgG geometric mean titers (GMT) among booster vaccinees were 2,201 BAU/mL which were higher by nine-fold and 4.6-fold than those in primary Pfizer-BioNTech vaccinees (236 BAU/mL), and mRNA-1273 vaccinees (479 BAU/mL), respectively.
Additionally, booster doses induced substantially greater S IgG titers among cord blood samples (GMT 3,290 BAU/mL) which were higher by nine-fold than those in primary Pfizer--BioNTech vaccinees (GMT 369 BAU/mL) and by 4.2-fold than primary mRNA-1273 vaccinees (GMT 792 BAU/mL). Identical trends were observed for S and S RBD binding antibody titers in cord blood during the follow-up visits.
Binding antibody titers to S and S RBD were higher among booster vaccinees by 0.6 log10 at delivery than the combined doses of primary vaccines (m-1273 and Pfizer--BioNTech vaccinees) after data adjustments for time elapsed since the previous vaccination. Substantially greater nAb titers against D614G were observed post-vaccination among booster vaccinees (ID50 630) than the primary vaccinees (ID50 62 and 193 for Pfizer--BioNTech and mRNA-1273 vaccinees, respectively).
The nAb titers remained higher during delivery among all booster vaccinees (ID50 446) in comparison to 68% of the primary Pfizer--BioNTech vaccinees (ID50 50) and 96% of the primary mRNA-1273 vaccinees (ID50 180). At delivery, Omicron nAb titers were detected among merely 9% of Pfizer vaccinees (ID50 13) and 22% of mRNA-1273 vaccinees (ID50 15). On the contrary, 73% of booster vaccinees (ID50 60) demonstrated nAb titers for Omicron BA.1. Delta neutralization was higher than D614G neutralization but lower than Omicron BA.1 neutralization.
Likewise, in the cord blood, nAb titers for D614G were substantially higher among booster vaccinees (ID50 743) than among primary Pfizer--BioNTech vaccinees (ID50 77) and mRNA-1273 vaccinees (ID50 135). Of note, nAb titers for Omicron were substantially greater among cord blood samples obtained from booster vaccinees (response rate 88%, ID50 109) than those obtained from primary Pfizer-BioNTech vaccinees (response rate 14%, ID50 13) or mRNA-1273 vaccinees (response rate 22%, ID50 15). Transplacental antibody transfer was efficient after the primary vaccinations and booster vaccinations, with meant transplacental transfer ratios ranging between 1.6 and 1.8 for binding antibodies and ranging between 1.0 and 1.8 for nAb.
To conclude, based on the study findings, primary and booster COVID-19 mRNA vaccinations must be continued to be administered to pregnant women.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.