Immunogenicity and reactogenicity of heterologous COVID-19 vaccination in pregnant women.

This open-labeled non-inferiority trial evaluated immunogenicity and reactogenicity of heterologous and homologous COVID-19 vaccination schedules in pregnant Thai women. 18-45-year-old pregnant women with no history of COVID-19 infection or vaccination and a gestational age of ≥12 weeks were randomized 1:1:1 into three two-dose primary series scheduled 4 weeks apart: BNT162b2-BNT162b2 (Group 1), ChAdOx1-BNT162b2 (Group 2), and CoronaVac-BNT162b2 (Group 3). Serum antibody responses, maternal and cord blood antibody levels at delivery, and adverse events (AEs) following vaccination until delivery were assessed. The 124 enrolled participants had a median age of 31 (interquartile range [IQR] 26.0-35.5) years and gestational age of 23.5 (IQR 18.0-30.0) weeks. No significant difference in anti-receptor binding domain (RBD) IgG were observed across arms at 2 weeks after the second dose. Neutralizing antibody geometric mean titers against the ancestral Wuhan strain were highest in Group 3 (258.22, 95% CI [187.53, 355.56]), followed by Groups 1 (187.47, 95% CI [135.15, 260.03]) and 2 (166.63, 95% CI [124.60, 222.84]). Cord blood anti-RBD IgG was correlated with, and equal to or higher than, maternal levels at delivery (r = 0.719, P < .001) and inversely correlated with elapsed time after the second vaccination (r = -0.366, P < .001). No significant difference in cord blood antibody levels between groups were observed. Local and systemic AEs were mild-to-moderate and more frequent in Group 2. Heterologous schedules of CoronaVac-BNT162b2 or ChAdOx1-BNT162b2 induced immunogenicity on-par with BNT162b2-BNT162b2 and may be considered as alternative schedules for primary series in pregnant women in mRNA-limited vaccine settings.

Immunogenicity and reactogenicity against the SARS-CoV-2 variants following heterologous primary series involving CoronaVac, ChAdox1 nCov-19 and BNT162b2 plus BNT162b2 booster vaccination: An open-label randomized study in healthy Thai adults.

We evaluated the immunogenicity and reactogenicity of heterologous COVID-19 primary schedules involving BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca) and CoronaVac (Sinovac) in healthy adults, as well as booster response to BNT162b2 following heterologous CoronaVac and ChAdOx1 nCoV-19 regimens. Participants were randomized to one of seven groups that received two-dose homologous BNT162b2 or heterologous combinations of CoronaVac, ChAdOx1 nCoV-19 and BNT162b2, with 4 weeks interval. A total of 210 participants were enrolled, 30 in each group. Median age of participants was 38 (19-60) years, and 108/210 (51.43%) were female. Overall adverse events after the second dose were mild to moderate. We found that groups that received BNT162b2 as second dose induced the highest anti-receptor binding domain IgG response against the ancestral strain [BNT162b2: geometric mean concentration (GMC) 2133-2249 BAU/mL; ChAdOx1 nCoV-19: 851-1201; CoronaVac: 137-225 BAU/mL], neutralizing antibodies (NAb) against Beta and Delta, and interferon gamma response. All groups induced low to negligible NAb against Omicron after second dose. A BNT162b2 booster (third dose) following heterologous CoronaVac and ChAdOx1 nCoV-19 regimens induced >140-fold increase in NAb titers against Omicron. Our findings indicate that heterologous regimens using BNT162b2 as the second dose may be an alternative schedule to maximize immune response. While heterologous two-dose schedules induced low NAb against Omicron, the use of an mRNA vaccine booster dose substantially increased the Omicron response. These findings are relevant for low-income countries considering heterologous primary and booster COVID-19 vaccine schedules.

Immunogenicity and reactogenicity of accelerated regimens of fractional intradermal COVID-19 vaccinations.

Introduction: This phase I study explored the immunogenicity and reactogenicity of accelerated, Q7 fractional, intradermal vaccination regimens for COVID-19. Methods: Participants (n = 60) aged 18-60 years, naïve to SARS-CoV-2 infection or vaccination, were randomly allocated into one of four homologous or heterologous accelerated two-dose, two-injection intradermal regimens seven days apart:(1) BNT162b2-BNT162b2(n= 20),(2) ChAdOx1- BNT162b2 (n = 20), (3) CoronaVac-ChAdOx1 (n = 10), and (4) ChAdOx1-ChAdOx1 (n = 10). CoronaVac and ChAdOx1 were 20%, and BNT162b2 17%, of their standard intramuscular doses (0.1 mL and 0.05 mL per injection, respectively). Humoral immune responses were measured through IgG response towards receptor binding domains (RBD-IgG) of ancestral SARS-CoV-2 spike protein and pseudovirus neutralization tests (PVNT50). Cellular immune responses were measured using ELISpot for ancestral protein pools. Results: Immunogenicity was highest in regimen (2), followed by (1), (4), and (3) 2 weeks after the second dose (P < 0.001 for anti-RBD-IgG and P= 0.01 for PVNT50). Each group had significantly lower anti-RBD IgG (by factors of 5.4, 3.6, 11.6, and 2.0 for regimens (1) to (4), respectively) compared to their respective standard intramuscular regimens (P < 0.001 for each). Seroconversion rates for PVNT50 against the ancestral strain were 75%, 90%, 57% and 37% for regimens (1) to (4), respectively. All participants elicited ELISpot response to S-protein after vaccination. Adverse events were reportedly mild or moderate across cohorts. Discussion: We concluded that accelerated, fractional, heterologous or homologous intradermal vaccination regimens of BNT162b2 and ChAdOx1 were well tolerated, provided rapid immune priming against SARS-CoV-2, and may prove useful for containing future outbreaks.