Boosting effects of additional mRNA COVID-19 vaccine given after one year in adults previously received two doses inactivated COVID-19 vaccines with third dose of any COVID-19 vaccine during Omicron XBB.1.5

Introduction: Whole inactivated vaccines (WIV) were among the first few vaccines available and used in developing countries as primary series especially had been used to control during early phase of SARSCoV2 pandemics. Surging of variants of concern (VOCs) and waning of immune responses after 3 months, subsequence booster doses of heterologous COVID-19 vaccines were recommended by giving the booster dose at the longer interval. The study investigate the boosting effects of bivalent mRNA COVID-19 vaccine given after 12 months during the omicron XBB epidemics to who had received the third dose of COVID-19 vaccine. Methods: A prospective, single-center, open-label, phase 2 study assessing immune responses both humoral and T-cell responses were conducted in those who had received two doses of inactivated COVID-19 vaccines with third or fourth dose of any COVID vaccines (adenovirus vector vaccine Ad26.COV2.S or ChAdOx1, the mRNA vaccine) and receiving bivalent mRNA COVID-19 (original/BA.4-5) vaccine as a booster dose after 12 months. Immune responses were measured by Anti-Spike IgG (GMFR), Pseudovirus neutralizing assay to ancestral, Omicron XBB strain (GMT 50%NT, GMFR) and IFN-Gamma (mIU/mL, Median) at day 0, 28 and 90. Results: 198 enrolled participants had received bivalent mRNA COVID-19 vaccine. 190 of 198 were analyzed. 57, 66 and 67 participants had previously received third dose with Ad26.COV2.S, ChAdOx1 and mRNA COVID-19 vaccines respectively. There were no safety concerns reported. No reported of COVID-19 symptomatic infection nor received another COVID-19 vaccine within 90 days of follow up. GMFR from baseline to day 28 and 90 were 6.62, 3.36 in Ad26.COV2.S group, 7.81, 4.04 in ChAdOx1 group and 7.52, 4.37 in mRNA group.Pseudo neutralizing antibody GMT (95% CI) against Ancestral strain at day 0, 28, 90 were 193(135-269), 1315(1095-1581), 1527(1260-1850) in Ad26.COV2.S group 189(133-269), 1531(1356-1729), 1694(1485-1923) in ChAdOx1 group 165(110-248), 1629(1388-1913), 2078(1731-2494) in mRNA group. GMFR from baseline to day 28 and 90 were 6.55, 7.60 in Ad26.COV2.S group, 7.40, 8.18 in ChAdOx1 group and 8.45, 10.98 in mRNA group.Pseudo neutralizing antibody GMT against Omicron XBB 1.5 strain at day 0, 28, 90 were 28 (14-56), 792(624-1005), 327(263-407) in Ad26.COV2.S group 14(7-28), 867(867-1075), 332(228-483) in ChAdOx1 group 13(6.9-25), 1129(951-1340), 475(383-589) in mRNA. GMFR from baseline to day 28 and 90 were 13.04, 5.4 in Ad26.COV2.S group, 20.9, 8.03 in ChAdOx1 group and 29.16, 12.77 in mRNA group. Median IFN gamma day 0, 28, 90 were 1686, 4203, 2548 in Ad26.COV2.S group 1447, 5278, 3119 in ChAdOx1 group and 3244, 5913, 4984 in mRNA group Conclusion and Discussion: booster COVID-19 vaccine with bivalent mRNA (original/BA.4-5) after one year were safe and able to induce higher Immune response against Omicron XBB. Together with the infection, the hybrid immunity remained to be high up to day 90.