Humoral and cellular immunogenicity of homologous and heterologous booster vaccination in Ad26.COV2.S-primed individuals: Comparison by breakthrough infection.

Background: Whether or not a single-dose Ad26.COV2.S prime and boost vaccination induces sufficient immunity is unclear. Concerns about the increased risk of breakthrough infections in the Ad26.COV2.S-primed population have also been raised. Methods: A prospective cohort study was conducted. Participants included healthy adults who were Ad26.COV2.S primed and scheduled to receive a booster vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S. The IgG anti-receptor binding domain (RBD) antibody titers, neutralizing antibody (NAb) titers (against wild type [WT] and Omicron [BA.1 and BA.5]), and Spike-specific interferon-γ responses of the participants were estimated at baseline, 3-4 weeks, 3 months, and 6 months after booster vaccination. Results: A total of 89 participants were recruited (26 boosted with BNT162b2, 57 with mRNA-1273, and 7 with Ad26.COV2.S). The IgG anti-RBD antibody titers of all participants were significantly higher at 6 months post-vaccination than at baseline. The NAb titers against WT at 3 months post-vaccination were 359, 258, and 166 in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. Compared with those against WT, the NAb titers against BA.1/BA.5 were lower by 23.9/10.9-, 16.6/7.4-, and 13.8/7.2-fold in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively, at 3 months post-vaccination. Notably, the NAb titers against BA.1 were not boosted after Ad26.COV2.S vaccination. Breakthrough infections occurred in 53.8%, 62.5%, and 42.9% of the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. No significant difference in humoral and cellular immunity was found between individuals with and without SARS-CoV-2 breakthrough infections. Conclusion: Booster vaccination elicited acceptable humoral and cellular immune responses in Ad26.COV2.S-primed individuals. However, the neutralizing activities against Omicron subvariants were negligible, and breakthrough infection rates were remarkably high at 3 months post-booster vaccination, irrespective of the vaccine type. A booster dose of a vaccine containing the Omicron variant antigen would be required.

Transmission and Infectious SARS-CoV-2 Shedding Kinetics in Vaccinated and Unvaccinated Individuals.

Importance: Data are limited on whether patients with breakthrough COVID-19 infection have the potential to significantly contribute to the spread of SARS-CoV-2. Objective: To compare the secondary attack rate and infectious viral shedding kinetics of SARS-CoV-2 between fully vaccinated individuals (breakthrough infection group) and partially or unvaccinated individuals (nonbreakthrough infection group). Design, Setting, and Participants: This cohort study assessed secondary transmission by analyzing the epidemiologic data of health care workers, inpatients, and caregivers diagnosed with COVID-19 during hospitalization or residence in a tertiary care hospital between March 1, 2020, and November 6, 2021. To evaluate viral shedding kinetics, the genomic RNA of SARS-CoV-2 was measured using polymerase chain reaction and performed virus culture from daily saliva samples of individuals with mild COVID-19 infected with the Delta variant who were isolated in a community facility in Seoul, South Korea, between July 20 and August 20, 2021. Exposures: COVID-19 vaccination. Main Outcomes and Measures: The secondary attack rate and infectious viral shedding kinetics according to COVID-19 vaccination status. Results: A total of 173 individuals (median [IQR] age, 47 [32-59] years; 100 female [58%]) with COVID-19 were included in the secondary transmission study, of whom 50 (29%) had a breakthrough infection. Secondary transmission was significantly less common in the breakthrough infection group than in the nonbreakthrough infection group (3 of 43 [7%] vs 29 of 110 [26%]; P = .008). In the viral shedding kinetics study, 45 patients (median age, 37 years [IQR, 25-49 years]; 14 female [31%]) infected with the Delta variant were included, of whom 6 (13%) were fully vaccinated and 39 (87%) were partially or unvaccinated. Although the initial genomic viral load was comparable between the 2 groups, viable virus in cell culture was detected for a notably longer duration in partially vaccinated (8 days after symptom onset) or unvaccinated (10 days after symptom onset) individuals compared with fully vaccinated individuals (4 days after symptom onset). Conclusions and Relevance: In this cohort study, although the initial genomic viral load was similar between vaccinated and unvaccinated individuals, fully vaccinated individuals had a shorter duration of viable viral shedding and a lower secondary attack rate than partially vaccinated or unvaccinated individuals. Data from this study provide important evidence that despite the possibility of breakthrough infections, COVID-19 vaccinations remain critically useful for controlling the spread of SARS-CoV-2.

Insights into the immune responses of SARS-CoV-2 in relation to COVID-19 vaccines.

The three types of approved coronavirus disease 2019 (COVID-19) vaccines that have been emergency-use listed (EUL) by the World Health Organization are mRNA vaccines, adenovirus-vectored vaccines, and inactivated vaccines. Canonical vaccine developments usually take years or decades to be completed to commercialization; however, the EUL vaccines being used in the current situation comprise several COVID-19 vaccine candidates applied in studies and clinical settings across the world. The extraordinary circumstances of the COVID-19 pandemic have necessitated the emergency authorization of these EUL vaccines, which have been rapidly developed. Although the benefits of the EUL vaccines outweigh their adverse effects, there have been reports of rare but fatal cases directly associated with COVID-19 vaccinations. Thus, a reassessment of the immunological rationale underlying EUL vaccines in relation to COVID-19 caused by SARSCOV-2 virus infection is now required. In this review, we discuss the manifestations of COVID-19, immunologically projected effects of EUL vaccines, reported immune responses, informed issues related to COVID-19 vaccination, and the potential strategies for future vaccine use against antigenic variants.