Homologous or heterologous administration of mRNA or adenovirus-vectored vaccines show comparable immunogenicity and effectiveness against the SARS-CoV-2 Omicron variant

ABSTRACT

Background

Heterologous prime-boost schedules have been employed in SARS-CoV-2 vaccination, yet additional data on immunogenicity and effectiveness are still needed.

Research design and methods

Here, we measured the immunogenicity and effectiveness in the real-world setting of the mRNA booster dose in 181 subjects who had completed primary vaccination with ChAdOx1, BNT162b2, or mRNA1273 vaccines (IMMUNO_COV study; protocol code 18,869). The spike-specific antibody and B cell responses were analyzed up to 6 months after boosting.

Results

After an initial slower antibody response, the heterologous ChAdOx1/mRNA prime-boost formulation elicited spike-specific IgG titers comparable to homologous approaches, while spike-specific B cells showed a higher percentage of CD21⁻CD27⁻ atypical cells compared to homologous mRNA vaccination. Mixed combinations of BNT162b2 and mRNA-1273 elicited an immune response comparable with homologous strategies. Non-significant differences in the Relative Risk of infection, calculated over a period of 18 months after boosting, were reported among homologous or heterologous vaccination groups, indicating a comparable relative vaccine effectiveness.

Conclusions

Our data endorse the heterologous booster vaccination with mRNA as a valuable alternative to homologous schedules. This approach can serve as a solution in instances of formulation shortages and contribute to enhancing vaccine strategies for potential epidemics or pandemics.

KEYWORDS:

• COVID-19 vaccination
• heterologous and homologous vaccination
• prime-boost
• SARS-CoV-2
• vaccination strategies

Article highlights

• The heterologous combination of ChAdOx1 for the first vaccination cycle with BNT162b2 or mRNA-1273 vaccines for boosting elicits a spike-specific antibody response comparable to the homologous strategy using mRNA vaccines.

• Mixing the BNT162b2 and mRNA-1273 for priming and boosting and vice versa does not alter the immune response compared to repeated doses with the same mRNA vaccine.

• BNT162b2 and mRNA-1273 vaccines have shown a comparable immunogenicity and effectiveness when used as booster formulation.

• The heterologous prime – boost strategies can be a valuable alternative approach to homologous schedules, against SARS-CoV-2 and possibly other pathogens.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Informed consent statement

Informed consent was obtained from all subjects involved in the study.

Author contributions

AC, GP, FM and DM conceived the study. IR, AL, MD, MF, MT and FM. enrolled patients. GP, JP, and SZ processed the samples. GP, FF, JP and SZ carried out the immunological analysis. AC, GP, FF, JP, SL and GM analyzed the data. AC, GP and DM wrote the manuscript. AC, GP and DM supervised the study. DM provided financial support. All the authors have substantially contributed to the conception and design of the article and interpreting the relevant literature and been involved in writing the article or revised it for intellectual content

Data availability statement

Data available upon request.

Additional information

Funding

This manuscript was funded by the European Union-Next Generation EU, in the context of The National Recovery and Resilience Plan (PNRR), Project Tuscany Health Ecosystem (THE), Spoke n. 7 “Innovating translational medicine”.