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Background: Immune responses to each vaccine must be investigated to establish effective vaccination strategies for the ongoing coronavirus disease (COVID-19) pandemic. We investigated the long-term kinetics of immune responses after heterologous booster vaccination in relation to Omicron breakthrough infection (BI). Methods: Our study included 373 healthcare workers who received primary ChAdOx1 vaccine doses and a third BNT162b2 vaccine dose. BIs that occurred after the third vaccine were investigated. Blood specimens were collected before and 3 months after the booster dose from participants without BI and 1, 4, and 6 months after BI from participants who experienced BI. Spike-specific binding and neutralizing antibody levels against the wild-type virus, Omicron BA.1, and Omicron BA.5, as well as cellular responses, were analyzed. Results: A total of 346 participants (82 in the no BI group; 192 in the BI group during the BA.1/BA.2 period; 72 in the BI group during the BA.5 period) were included in the analysis. Participants without BI exhibited the highest binding and neutralizing antibody concentrations and greatest cellular response 1 month after the third vaccination, which reached a nadir by the ninth month. Antibody and cellular responses in participants who experienced BI substantially increased postinfection. Neutralizing antibody titers in individuals who experienced BI during the BA.1/BA.2 period showed more robust increase against wild-type virus than against BA.1 and BA.5. Conclusions: Our findings provide evidence of antigenic imprinting in participants who received a heterologous booster vaccination, thereby serving as a foundation for further studies on the impact of BIs on immune responses.

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Background: There are few studies reported on the acceptance of heterologous booster vaccination for the COVID-19 vaccine among healthcare workers (HCWs) and the general population. We aimed to address that gap and explore determinant factors of acceptance of the heterologous booster vaccination. Methods: We conducted a cross-sectional study to examine the prevalence and determinant factors of the acceptance of heterologous booster vaccination for the COVID-19 vaccine among HCWs and the targeted population. Results: A total of 364 HCWs and 1,898 targeted populations were investigated in our study. 76.4% HCWs would recommend heterologous booster vaccination to their patients and 59.8% targeted population endorsed a clear willingness to receive this strategy. Compared with the adenoviral vector vaccine (AD5-nCOV), recombinant protein vaccine (ZF2001) was more preferred by HCWs (79.1%) and the targeted population (72.0%) as a heterologous booster vaccine. HCWs who did not work in the vaccination clinics were more likely to recommend heterologous booster vaccination (OR = 3.3, CI: 1.5-7.3). The targeted population aged 18-59 years (OR = 1.5, 95% CI:1.1-2.3), had a positive attitude toward COVID-19 vaccination (OR = 3.8, 95% CI: 1.7-8.6), had confidence in the safety of COVID-19 vaccines (OR = 6.6, 95% CI: 4.2-10.2), followed the recommendation of HCWs (OR = 33.6, 95% CI: 22.0-51.2), took initiative in collecting booster shots information (OR = 2.1, 95% CI: 1.5-3.0), and were familiar with the heterologous strategy (OR = 1.9, 95% CI: 1.1-3.1) were more likely to choose heterologous booster vaccination. The history of side effects of inactivated COVID-19 vaccine was a negative factor in choosing heterologous booster vaccination (OR = 0.4, 95% CI: 0.4-1.0). Conclusions: The heterologous booster vaccination strategy on the COVID-19 vaccine could be widely accepted among HCWs, whereas its acceptance among targeted population was only moderate. Public authorities should make efforts to communicate the public about the effectiveness and safety of the heterologous booster vaccination which could help increase their willingness to get vaccinated.

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Information on the effects of a heterologous booster in adult patients first vaccinated with the BBIBP-CorV vaccine is limited. This prospective cohort study evaluated the humoral response of 152 healthcare workers (HCWs) from a private laboratory in Lima (Peru) before and after receiving the BNT162b2 vaccine, with a seven-month interval since the BBIBP-CorV doses. We employed the Elecsys® anti-SARS-CoV-2 S and the cPass™ SARS-CoV-2 Neutralization Antibody (NAbs) assays to evaluate anti-S-RBD IgG and NAbs, respectively. Of the 152 HCWs, 79 (51.98%) were previously infected (PI) with SARS-CoV-2 and 73 (48.02%) were not previously infected (NPI). The proportion of HCWs with positive NAbs, seven months after the BBIBP-CorV immunization, was 49.31% in NPI and 92.40% in PI. After the booster, this ratio increased to 100% in both groups. The anti-S-RBD IgG and NAbs in the HCWs' NPI increased by 32.7 and 3.95 times more, respectively. In HCWs' PI, this increment was 5 and 1.42 times more, respectively. There was no statistical association between the history of previous SARS-CoV-2 infection and the titer of anti-S-RBD IgG and NAbs after the booster. The humoral immunity presented a robust increase after receiving the BNT162b2 booster and was more pronounced in NPI.

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Patients with haemato-oncological malignancies are one of the high-risk groups for a severe course in case of COVID-19 infections. Furthermore, vaccination results in significantly lower response rates in haematological malignancies and lower antibody levels in patients with solid cancer. We investigated efficacy and safety of a heterologous booster vaccination with Ad26.COV2.S DNA vector vaccine in haemato-oncological patients without antibody response after double-dose BNT162b2 messenger (m-)RNA COVID-19 vaccine. A total of 32 haemato-oncological non-responders to double-dose BNT162b2 received a heterologous booster vaccination with Ad26.COV2.S. Blood samples were assessed directly before the vaccination (T0) and four weeks after (T1). Safety assessment was performed using a standardised questionnaire. The overall response rate was 31%, with a mean (SD) antibody titre of 693·79 (1 096·99) binding activity units (BAU)/ml. Patients with chronic lymphocytic leukaemia or lymphoma showed a significantly lower response rate (P = 0·048). Adverse events were reported in 29·6% of patients, of which 7·1% were graded as severe, including grade III and IV events following the Common Terminology Criteria of Adverse Events (CTCAE). The heterologous booster vaccination with Ad26.COV2.S led to a serological response in nine out of 29 patients without response after double-dose BNT162b2. Furthermore, the vaccination was safe in our cohort, leading to mainly mild local and systemic reactions. Overall, this vaccination regimen should be further evaluated to increase the response rate in the highly vulnerable population of haemato-oncological patients.

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