Study of efficacy and antibody duration to fourth-dose booster of Ad5-nCoV or inactivated SARS-CoV-2 vaccine in Chinese adults: a prospective cohort study

Abstract

Introduction: China experienced a record surge of coronavirus disease 2019 cases in December 2022, during the pandemic.

Methods: We conducted a randomized, parallel-controlled prospective cohort study to evaluate efficacy and antibody duration after a fourth-dose booster with Ad5-nCoV or inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine.

Results: A total of 191 participants aged ≥18 years who had completed a three-dose regimen of the inactivated SARS-CoV-2 vaccine 6 months earlier were recruited to receive the intramuscular Ad5-nCoV booster or the inactivated SARS-CoV-2 vaccine. The Ad5-nCoV group had significantly higher antibody levels compared with the inactivated vaccine group at 6 months after the fourth vaccination dose. After the pandemic, the breakthrough infection rate for the Ad5-nCoV and the inactivated vaccine groups was 77.89% and 78.13%, respectively. Survival curve analysis (p = 0.872) and multivariable logistic regression analysis (p = 0.956) showed no statistically significant differences in breakthrough infection between the two groups.

Discussion: Compared with a homologous fourth dose, a heterologous fourth dose of Ad5-nCoV elicited a higher immunogenic response in healthy adults who had been immunized with three doses of inactivated vaccine. Nevertheless, the efficacy of the two vaccine types was equivalent after the pandemic.

Keywords: Ad5-nCoV; COVID-19; SARS-CoV-2; breakthrough infection; fourth dose.

Figure 1

Trial profile. A total of 211 volunteers were recruited and screened for eligibility. Overall, 201 participants were enrolled and randomly assigned, 200 participants received the booster dose vaccination, and one participant withdrew voluntarily after randomization. Participants in each group (n = 96 and n = 95) completed both the planned visits at 6 months after vaccination and the telephone follow-up in March 2023.

Figure 2

Antibody responses before and after booster vaccination. ID50 of SARS-CoV-2 RBD-specific IgG antibodies (A) and ID50 of pseudovirus-neutralizing antibodies against Omicron BA.4/5 (B) on day 0 (before booster vaccination) and at 6 months after booster vaccination in the inactivated SARS-CoV-2 vaccine group and the Ad5-nCoV group. ID50 of SARS-CoV-2 RBD-specific IgG antibodies (C) and ID50 of pseudovirus-neutralizing antibodies against Omicron BA.4/5 (D) at 6 months after booster vaccination in the inactivated SARS-CoV-2 vaccine group and the Ad5-nCoV group with different age subgroups. GMFIs of SARS-CoV-2 RBD-specific IgG antibodies (E) and GMFIs of pseudovirus-neutralizing antibodies against Omicron BA.4/5 (F) at 6 months after booster vaccination in the inactivated SARS-CoV-2 vaccine group and the Ad5-nCoV group. ns, no significance; ^* P < 0.05; ^** P < 0.01; ^*** P < 0.001.

Figure 3

Epidemiologic curve of breakthrough cases. Daily numbers of confirmed cases, suspected cases, and asymptomatic cases. In March 2023, the participants were followed up by telephone to collect information on breakthrough infection. The breakthrough infection occurred from 13 December 2022 to 16 January 2023. Peak occurred between 20 December 2022 and 26 December 2022, counted 47.12% (90/191) during this time.

Figure 4

Survival curves of breakthrough infection. The Cox model estimate shows the cumulative probability of breakthrough infection by vaccination type adjusted for sex, age, chronic diseases, and influenza vaccine history, starting on 12 December 2022.

Figure 5

Breakthrough symptoms of the two vaccine groups. The incidence of fever in the Ad5-nCoV group (54.74%) was lower than that in the inactivated vaccine group (71.88%, p = 0.014); the incidence of high fever especially was lower in the Ad5-nCoV group (7.37%) than that in the inactivated vaccine (27.08%, p < 0.001). *p < 0.05; ***p < 0.001.