Mother's Pregnancy Trimester Does Not Affect the Differences of IgG SARS-COV-2 Antibody Levels in Pregnant Women after mRNA and Inactivated Coronavirus Disease 2019 Vaccination

BACKGROUND: Since pregnancy increases the risk of coronavirus disease 2019 (COVID-19) and its morbidity in pregnant women, it is necessary and recommended to prevent COVID-19 in pregnant women by vaccination such as by messenger RNA (mRNA) and inactivated vaccines. SARS-CoV-2 antibodies produced from vaccination have different results according to the type of vaccine given. The previous studies showed that IgG SARS-CoV-2 antibody levels were influenced by various factors such as gestational weeks at the time when vaccines were given. Moreover, there have been no previous studies on the effect of gestational age on quantitative IgG levels after the second dose of the vaccine especially in Indonesia during this pandemic due to some restrictions on daily activities. AIM: The aim of this study is to see the effect of giving the COVID-19 vaccine based on maternal gestational age (in trimester units) on maternal immunity (IgG SARS-CoV-2) in Dr. Hasan Sadikin General Hospital Bandung, Bandung Kiwari Hospital and Dr. Slamet Hospital, Garut. METHOD(S): This was a retrospective and cohort study by taking secondary data using consecutive sampling from the previous tests on the levels of SARS-CoV-2 IgG antibodies after two doses of inactivated vaccine and mRNA. Healthy pregnant women 14-34 weeks at the Department of Obstetrics and Gynecology, Dr. Hasan Sadikin (RSHS) Bandung, Bandung Kiwari Hospital, and Dr. Slamet Hospital for the period October 2021 to January 2022 were the target population of this study. Based on inclusion and exclusion criteria, 103 samples met the criteria. Examination of Maternal SARS-CoV-2 IgG Antibody Levels procedures was carried out using Chemiluminescent Microparticle Immunoassay. Statistical analysis was done using IBM SPSS 28.00 and p < 0.05 was considered statistically significant. RESULT(S): There was no significant difference (p = 0.236, p > 0.05) between the mean maternal age in the mRNA and inactivated vaccine groups. The mRNA and inactivated vaccine groups also had no significant difference in the gestational age category (0.70). There was a significant difference (p = 0.0001) between the levels of SARS-CoV-2 IgG antibodies after the vaccine in the mRNA and inactivated vaccine groups. There was no significant difference in the levels of SARS-CoV-2 IgG antibodies in the gestational age group after the mRNA vaccine (p = 0.426) and after the inactivated vaccine (p = 0.293). There was a significant difference (p < 0.05) in the subgroup analysis in each gestational age group (second trimester and third trimester) between SARS-CoV-2 IgG antibody levels after the mRNA vaccine compared to inactivated vaccine. DISCUSSIONS: The mRNA vaccine is based on the principle that mRNA is an intermediate messenger to be translated to an antigen after delivery to the host cell via various routes. However, inactivated vaccines contain viruses whose genetic material has been destroyed by heat, chemicals, or radiation, so they cannot infect cells and replicate but can still trigger an immune response. The administration of the vaccine in the second and third trimesters of pregnancy has the same results in increasing levels of SARS-CoV-2 IgG antibodies after mRNA and inactivated vaccination in this study. CONCLUSION(S): mRNA vaccination in pregnant women is better than inactivated vaccines based on the levels of IgG SARS-CoV-2 antibodies after vaccination. The maternal trimester of pregnancy was not a factor influencing the levels of SARS-CoV-2 IgG antibodies after either mRNA or inactivated COVID-19 vaccinations in this study.Copyright © 2023 Anita Deborah Anwar, Putri Nadhira Adinda Adriansyah, Ivan Christian Channel, Annisa Dewi Nugrahani, Febriani Febriani, Asep Surachman, Dhanny Primantara Johari Santoso, Akhmad Yogi Pramatirta, Budi Handono.

The kinetics of IgG subclasses and contributions to neutralizing activity against SARS-CoV-2 wild-type strain and variants in healthy adults immunized with inactivated vaccine.

Neutralizing antibody is an important indicator of vaccine efficacy, of which IgG is the main component. IgG can be divided into four subclasses. Up to now, studies analysing the humoral response to SARS-CoV-2 vaccination have mostly focused on measuring total IgG, and the contribution of specific IgG subclasses remains elusive. The aim of this study is to investigate the kinetics of neutralizing antibodies and IgG subclasses, and to explore their relationships in people vaccinated with inactivated COVID-19 vaccine. We conducted a prospective cohort study in 174 healthy adults aged 18-59 years old who were administrated 2 doses of CoronaVac 14 days apart and a booster dose 1 year after the primary immunization, and followed up for 15 months. Blood samples were collected at various time points after primary and booster immunization. We used live SARS-CoV-2 virus neutralizing assay to determine neutralizing ability against the wild-type strain and 4 variants (Beta, Gamma, Delta and Omicron) and ELISA to quantify SARS-CoV-2 RBD-specific IgG subclasses. The results showed that the 2-dose primary immunization only achieved low neutralizing ability, while a booster shot can significantly enhance neutralizing ability against the wild-type strain, Beta, Gamma, Delta and Omicron variants. IgG1 and IgG3 were the most abundant serum antibodies, and IgG2 and IgG4 were hardly detected at any time. The ratio of IgG1/IgG3 was positively associated with the neutralization ability. The underlying mechanism requires further exploration.

Immunogenicity and Safety of a 3-Dose Regimen of a SARS-CoV-2 Inactivated Vaccine in Adults: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

BACKGROUND: Control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic needs effective vaccines. METHODS: In a phase 2 randomized, double-blind, placebo-controlled trial, 500 adults aged 18-59 years or ≥60 years were randomized in 2:2:1 ratio to receive 3 doses of 5 µg or 10 µg of a SARS-CoV-2 inactivated vaccine, or placebo separated by 28 days. Adverse events (AEs) were recorded through day 28 after each dosing. Live virus or pseudovirus neutralizing antibodies, and receptor binding domain immunoglobulin G (RBD-IgG) antibody were tested after the second and third doses. RESULTS: Two doses of the vaccine elicited geometric mean titers (GMTs) of 102-119, 170-176, and 1449-1617 for the 3 antibodies in younger adults. Pseudovirus neutralizing and RBD-IgG GMTs were similar between older and younger adults. The third dose slightly (<1.5 fold) increased GMTs. Seroconversion percentages were 94% or more after 2 doses, which were generally similar after 3 doses. The predominant AEs were injection-site pain. All the AEs were grade 1 or 2 in intensity. No serious AE was deemed related to study vaccination. CONCLUSIONS: Two doses of this vaccine induced robust immune response and had good safety profile. A third dose given 28 days after the second dose elicited limited boosting antibody response.

A phase III, observer-blind, randomized, placebo-controlled study of the efficacy, safety, and immunogenicity of SARS-CoV-2 inactivated vaccine in healthy adults aged 18-59 years: An interim analysis in Indonesia.

BACKGROUND: The WHO declared COVID-19 a pandemic on March 11th, 2020. This serious outbreak and the precipitously increasing numbers of deaths worldwide necessitated the urgent need to develop an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. The development of COVID-19 vaccines has moved quickly. In this study, we assessed the efficacy, safety, and immunogenicity of an inactivated (SARS-CoV-2) vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate the efficacy, immunogenicity, and safety of an inactivated SARS-CoV-2 vaccine and its lot-to-lot consistency. A total of 1620 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine or placebo on a day 0 and 14 schedule. This article was based on an interim report completed within 3 months following the last dose of study vaccine. The interim analysis includes safety and immunogenicity data for 540 participants in the immunogenicity subset and an efficacy analysis of the 1620 subjects. For the safety evaluation, solicited and unsolicited adverse events were collected after the first and second vaccination within 14 and 28 days, respectively. Blood samples were collected for an antibody assay before and 14 days following the second dose. RESULTS: Most of the adverse reactions were in the solicited category and were mild in severity. Pain at the injection site was the most frequently reported symptom. Antibody IgG titer determined by enzyme-linked immunosorbent assay was 97.48% for the seroconversion rate. Using a neutralization assay, the seroconversion rate was 87.15%. The efficacy in preventing symptomatic confirmed cases of COVID-19 occurring at least 14 days after the second dose of vaccine using an incidence rate was 65.30%. CONCLUSIONS: From the 3-month interim analysis, the vaccine exhibited a 65.30% efficacy at preventing COVID-19 illness with favorable safety and immunogenicity profiles.