» Articles » PMID: 34001897

Heterologous Vaccination Regimens with Self-amplifying RNA and Adenoviral COVID Vaccines Induce Robust Immune Responses in Mice

Abstract

Several vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1 CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.

Citing Articles

Strong immune responses and robust protection following a novel protein in adjuvant tuberculosis vaccine candidate.

Korompis M, De Voss C, Li S, Richard A, Salman Almujri S, Ateere A Sci Rep. 2025; 15(1):1886.

PMID: 39805855 PMC: 11729893. DOI: 10.1038/s41598-024-84667-8.


Alphaviral backbone of self-amplifying RNA enhances protein expression and immunogenicity against SARS-CoV-2 antigen.

Casmil I, Bathula N, Huang C, Wayne C, Cairns E, Friesen J Mol Ther. 2025; 33(2):514-528.

PMID: 39741413 PMC: 11852984. DOI: 10.1016/j.ymthe.2024.12.055.


Heterologous mRNA/MVA delivering trimeric-RBD as effective vaccination regimen against SARS-CoV-2: COVARNA Consortium.

Marcos-Villar L, Perdiguero B, Lopez-Bravo M, Zamora C, Sin L, Alvarez E Emerg Microbes Infect. 2024; 13(1):2387906.

PMID: 39087555 PMC: 11313003. DOI: 10.1080/22221751.2024.2387906.


Heterologous booster vaccination enhances antibody responses to SARS-CoV-2 by improving Tfh function and increasing B-cell clonotype SHM frequency.

Song Y, Wang J, Yang Z, He Q, Bao C, Xie Y Front Immunol. 2024; 15:1406138.

PMID: 38975334 PMC: 11224535. DOI: 10.3389/fimmu.2024.1406138.


Non-Glycosylated SARS-CoV-2 Omicron BA.5 Receptor Binding Domain (RBD) with a Native-like Conformation Induces a Robust Immune Response with Potent Neutralization in a Mouse Model.

Wongnak R, Brindha S, Oba M, Yoshizue T, Islam M, Islam M Molecules. 2024; 29(11).

PMID: 38893549 PMC: 11173568. DOI: 10.3390/molecules29112676.


References
1.
Ewer K, Barrett J, Belij-Rammerstorfer S, Sharpe H, Makinson R, Morter R . T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nat Med. 2020; 27(2):270-278. DOI: 10.1038/s41591-020-01194-5. View

2.
van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham J, Port J . ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature. 2020; 586(7830):578-582. PMC: 8436420. DOI: 10.1038/s41586-020-2608-y. View

3.
Voysey M, Clemens S, Madhi S, Weckx L, Folegatti P, Aley P . Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2020; 397(10269):99-111. PMC: 7723445. DOI: 10.1016/S0140-6736(20)32661-1. View

4.
Lee W, Wheatley A, Kent S, DeKosky B . Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat Microbiol. 2020; 5(10):1185-1191. DOI: 10.1038/s41564-020-00789-5. View

5.
Rydyznski Moderbacher C, Ramirez S, Dan J, Grifoni A, Hastie K, Weiskopf D . Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity. Cell. 2020; 183(4):996-1012.e19. PMC: 7494270. DOI: 10.1016/j.cell.2020.09.038. View