Assessment of safety and immunogenicity of a protein subunit COVID-19 vaccine (ABDALA) in pregnant women: a single-cohort, multicenter, observational ESPIRTA study.

BACKGROUND: Pregnant and lactating women are generally excluded from clinical trials during vaccine development. While the safety, inmunogenicity, efficacy, and effectiveness of the Abdala vaccine against COVID-19 have been demonstrated in the general population, there is a lack of specific information regarding its benefits for pregnant women. Consequently, this study was undertaken to evaluate the safety of the Abdala vaccine in pregnant women and their newborns, as well as to assess the maternal immune response elicited by the vaccination and its capacity for passive immunity transfer to the newborn.

METHODS: A simple cohort observational multicenter study was conducted across five maternity hospital in Havana City, Cuba. A hybrid approach was employed, integrating both retrospective and prospective data collection methods. The study analyzed all events occurring from the first dose of the Abdala vaccine during pregnancy, delivery, and the postpartum period, as well as those related to the fetus-/neonate. To provide contextual data from our settings as a reference for descriptive analyses, statistical information concerning some pregnancy-related and fetal-neonatal events from the same five maternity hospitals in the year 2020 was utilized (historical data). Immunogenicity analyses were conducted in a subgroup of participants from a single maternity hospital, measuring antibodies against the receptor-binding domain of SARS-CoV-2 (Anti-RBD IgG antibodies) and neutralizing antibodies (Nab) against two SARS-CoV-2 strains (D614G and Omicron B.1.1.529) were measured in both maternal and umbilical cord sera. Additionally, anti-IgA antibodies were evaluated in a colostrum samples. Antibody transfer across the placenta and breast milk was also analyzed. Various comparisons were made regarding gestational age at birth, vaccination trimester, timing from vaccination to delivery, and receipt of a booster dose, among other analyses. A formal sample size estimate was not made. Pregnant women who attended the aforementioned hospitals and met the established criteria were included in the study cohort. Descriptive statistics were utilized to characterize the study population. The Wilcoxon sum rank test was used for most immunological evaluations, while logistic regression analyses estimated the effects of different variables. The correlation between anti-RBD IgG titers in maternal and umbilical cord sera was assessed using Pearson's correlation coefficient. All statistical tests were performed at a significance level of p < 0.05.

RESULTS: The study was conducted in five Cuban hospitals from December 2021 to June 2022, involving a total of 940 pregnant women women who received the Abdala vaccine during their pregnancy. The common adverse events reported within the 72 h post-vaccination with the Abdala vaccine were consistent with previous findings using this vaccine in clinical trials and widespread vaccination campaigns in the general population, predominantly presenting as pain at the injection site (4.9%), somnolence (2.6%), and headache (2.3%). All reported events were of mild intensity. In terms of maternal morbidity, the predominant event noted was SARS-CoV-2 infection, with 83 cases (8.83%), primarily categorized as asymptomatic cases or exhibiting mild symptomatic disease. Overall, IgA titers were detected in 202 colostrum samples, with GMT of 1,227 (95% CI 986; 1,527). High anti-RBD IgG titers were found in 189 maternal and 231 umbilical cord blood samples, with GMT of 1,392.15 (95% CI 1,174; 1,651) and 1,923 (95% CI 1,625; 2,275) respectively. The placental transfer ratio (PTR) of anti-RBD IgG titers had a median of 1.54 (IQR 1.48), indicating effective transfer. The PTR of NAb exceeded 1 for both D614G and Omicron (B.1.1.529), being significantly higher in full-term newborns compared to premature newborns.

CONCLUSIONS: The ESPIRTA study provides valuable information concerning the application of the Abdala vaccine in specific populations, such as pregnant women, which was not available prior to this study. The safety evaluation of the Abdala vaccine during pregnancy, delivery and the puerperium, as well as in fetus-newborn, revealed no safety signals, as indicated by this cohort study. Elevated anti-RBD IgG titers were detected, in both in maternal serum and cord samples, indicating a positive correlation between them. Moreover, an efficient transfer of IgG antibodies across the placenta was demonstrated. The high anti-IgA titers found in the colostrum may provide an additional advantage regarding the passive transfer of antibodies from mother to newborn through breastfeeding. Furthermore, neutralizing antibodies against two SARS-CoV-2 strains, D614 G and the more recent Omicron B.1.1.529 variant, were identified. Further research is recommended to assess the long-term safety and efficacy of the Abdala vaccine for pregnant women and their newborns.