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Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule with mRNA and Inactivated COVID-19 Vaccines: A Single-Blinded, Randomized, Parallel Group Superiority Trial
17 Pages Posted: 11 Jan 2023
More...Abstract
Background: This study aimed to compare the immunogenicity of the heterologous prime-boost CoronaVac/BNT162b2 vaccination to the homologous CoronaVac/CoronaVac regimen.
Methods: We conducted a simple-blinded randomized superiority trial to measure SARS-CoV-2 neutralization antibodies and anti-spike receptor binding domain (RBD) IgG concentrations in blood samples collected in participants who had received the first dose of CoronaVac vaccine followed by a dose of BNT162b2 or CoronaVac vaccine. Participants were consenting adults with no or well-controlled comorbidities excluding any immune deficiency and without a history of symptoms suggestive of COVID-19 or positive COVID-19 test. The primary end point for immunogenicity was the serum neutralizing antibody level with a percentage of inhibition at 90% at 21-35 days after boost. A difference of 25% between groups was considered clinically relevant.
Findings: Among the 240 eligible participants, the primary end point data were available for 100 participants randomly allocated to heterologous boost group versus 99 participants randomly allocated to homologous boost dose group. Heterologous prime-boost regimen elicited significantly higher levels of neutralizating antibodies (median level of 94%, interquartile range (IQR) [81-96] versus median level of 96%, IQR [95-97]) and anti-spike IgG antibodies (median level of 13460, IQR [2557-29930] versus median level of 1190, IQR [347-4964]) compared to the homologous group. Accordingly, the percentage of subjects with a percentage of neutralizing antibodies> 90% was significantly higher in the heterologous group (90·0%) versus the homologous (60·6%). Interestingly, no severe events were noted within 30 days after the second dose of vaccination in both groups. Side effects were, however, significantly more frequent in the CoronaVac/CoronaVac group compared to the CoronaVac/Pfizer group (67·7% versus 42·0%, p<0·0001).
Interpretation: Our data reported the superiority of the heterologous prime-boost CoronaVac/BNT162b2 vaccination compared to the homologous CoronaVac/CoronaVac regimen in terms of immunogenicity thus constituting a proof of concept study supporting the use of inactivated vaccines in a heterologous mix-and-match strategy while ensuring good immunogenicity and safety.
Funding: Pasteur Institute of Tunis - We acknowledges the support of the staff of Pasteur Institute of Tunis specially Omar Baccouche, Leoni Mateur Group, Tunisian Electricity and Gas Company (STEG, Company headquarters) and Géant group as well the Tunisian Ministry of Health and the Tunisian Ministry of Social Care. We also thank the Tunisian National Committee for the Protection of Persons and the Tunisian Directorate of pharmacy and drugs.
Declaration of Interests: All authors declare no competing interests.
Ethics Approval: The study protocol was approved by the Tunisian National Committee for the Protection of Persons. All participants had adequate time to understand the study and voluntarily dated and signed the informed consent form. They reserved the right to withdraw from the study at any time.
Trial Registrations: The trial was registered under the reference numbers: TN2021-NAT-INS-70 and NCT05668065.
Suggested Citation: Suggested Citation