Immunogenicity and safety of recombinant novel coronavirus vaccine (CHO cell) after two doses of inactivated SARS-CoV-2 vaccine in healthy adults
ZHANG Shang-xiao1, YANG Shi-long2, HUANG Tao1, ZHONG Zai-xin2, ZHAO Jun-shi1, LI Xu1, DAI De-fang1, HU Chun-sheng1, SUN Jiu-feng3, GAO Li-dong1
1. Hunan Provincial Center for Disease Control and Prevention/Hunan Workstation for Emerging Infectious Disease Control and Prevention, Chinese Academy of Medical Sciences, Changsha, Hunan 410005, China;
2. Anhui Zhifei Longcom Biopharmaceutical Co., Ltd, Hefei, Anhui 230088, China;
3. Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, Guangdong 511430, China
Abstract：Objective To evaluate the immunogenicity and safety of recombinant novel coronavirus vaccine (CHO cell) after sequential immunization in population inoculated with two doses of inactivated SARS-CoV-2 vaccine so as to provide a scientific basis for formulating the enhanced immunization strategy of the SARS-CoV-2 vaccine. Methods Open experimental design was used to screen 360 subjects aged 18 and above who had been inoculated with two doses of new coronavirus inactivated vaccine for 3-4 months, 6-8 months, 11-13 months and one dose of recombinant novel coronavirus vaccine (CHO cell). Blood samples of all subjects before and 14 days after vaccination were collected for humoral immunity test, and all adverse events within one month after vaccination were collected. Results In this study, 360 subjects were divided into three groups according to the interval between fundamental immunity and booster (group A 91-120 days, group B 181-240 days, group C 331-390), 120 cases in each group, and no subject was dropped off. The mean age of the three groups was 38.13, 40.22 and 45.73 years, respectively, and the age difference among the groups was statistically significant (F=13.516, P<0.001). There was no significant difference between groups A and B (P=0.168), but the difference between groups C and A, B was statistically significant (both P<0.001). The IgG geometric mean concentration (GMC) of the three groups before booster immunization was 4.81 AU/ml, 4.23 AU/ml and 2.12 AU/ml, respectively, showing statistically significant differences (F=10.054, P<0.001). The differences between groups C and A, B were statistically significant (both P<0.001), but no statistically significant difference was found between groups A and B (P=0.520). The IgG GMC of the three groups after booster were 106.69 AU/ml, 124.05 AU/ml and 80.04 AU/ml, respectively, with no statistically significant difference (F=2.028, P=0.133). The positive conversion rates of IgG antibody in the three groups were 84.17%, 87.50% and 79.17%, respectively, and the difference was not statistically significant (χ2=3.081, P=0.214). Before booster immunization, the geometric mean titers (GMTs) of neutralizing antibodies in serumagainst prototype strains in the three groups were 1:2.18, 1:2.18 and 1:2.19, respectively, showing no statistically significant difference (F=0.011, P=0.990). The GMTs of neutralizing antibodies against delta mutant strains in the three groups were 1:2.09, 1:2.17 and 1:2.16, respectively, without statistically significant difference (F=0.378, P=0.686). After boosterimmunization, the GMTs of neutralizing antibodies in serum against prototype strains in the three groups were 1:31.09, 1:34.90 and 1: 21.98, respectively, without statistically significant difference (F=2.262, P=0.106). The GMTs of neutralizing antibodies against delta mutant strains in the three groups were 1:61.46, 1:77.44 and 1:43.71, respectively, showing no statisticallysignificant difference (F=2.105, P=0.123). After sequential immunization, the positive conversion rates of neutralizing antibodies in serum against delta mutant and prototype strains of new coronavirus reached 82.78% and 83.33%, respectively. The positive conversion rates of neutralizing antibody of SARS-CoV-2 prototype strains in the three groups were 86.67%, 87.50% and 75.83%, respectively, the difference was statistically significant (χ2=7.320, P=0.026), among which group C was lower than that in group A and group B. The positive conversion rate of neutralizing antibodies against SARS-CoV-2 delta variants in the three groups was 87.50%, 84.17% and 76.67%, respectively, with no significant difference (χ2=5.183, P=0.075). The number of adverse events was 124, and the overall incidence rate of adverse events was 34.44%. The incidence rates of adverse events in groups A, B and C were 35.83%, 40.83% and 26.67%, respectively, without statistically significant difference (χ2=5.487, P=0.064). The major adverse event found in all subjects occurred on vaccination site, with 23.89% of local pain. General adverse events mainly presented with fatigue or lacking of strength(6.94 %). No serious adverse events (SAEs) related to vaccination occurred. Conclusion After inoculation of two doses of inactivated SARS-CoV-2 vaccine, a sequential booster with recombinant novel coronavirus vaccine (CHO cell) has good immunogenicity and safety. The antibody level of IgG before booster immunization and the seroconversion rate of neutralizing antibody against prototype strains after booster immunization were lower in group of longer interval between fundamental immunization and booster immunization. There was no significant difference in theneutralizing antibody levels of IgG, delta mutant and prototype strains among different intervals. Six to eight months is recommended as an optimal interval of booster after fundamental immunization.
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2022, Vol. 29 
