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Randomized Immunogenicity and Safety Study of Heterologous Versus Homologous COVID-19 Booster Vaccination in Previous Recipients of Two Doses Of Coronavac COVID-19 Vaccine

32 Pages Posted: 30 Dec 2021

See all articles by Sue Ann Costa Clemens

Sue Ann Costa Clemens

University of Siena - Institute of Global Health

Lily Yin Weckx

Federal University of Sao Paulo

Ralf Clemens

affiliation not provided to SSRN

Ana Verena Almeida Mendes

affiliation not provided to SSRN

Alessandra Ramos Souza

affiliation not provided to SSRN

Mariana V. Silveira

affiliation not provided to SSRN

Suzete Nascimento Farias da Guarda

affiliation not provided to SSRN

Maristela Miyamotode Nobrega

affiliation not provided to SSRN

Maria Isabel de Moraes Pinto

affiliation not provided to SSRN

Isabela G. S. Gonzalez

affiliation not provided to SSRN

Natalia Salvador

affiliation not provided to SSRN

Marilia Miranda Franco

affiliation not provided to SSRN

Renata Navis de Avila Mendonça

affiliation not provided to SSRN

Isabelle Silva Queiroz Oliveira

affiliation not provided to SSRN

Bruno Solano de Freitas Souza

affiliation not provided to SSRN

Mayara Fraga

affiliation not provided to SSRN

Parvinder K. Aley

University of Oxford - Centre for Vaccinology and Tropical Medicine

Sagida Bibi

University of Oxford - Centre for Vaccinology and Tropical Medicine

Liberty Cantrell

University of Oxford

Teresa Lambe

University of Oxford - The Jenner Institute

Merryn Voysey

University of Oxford - Oxford Vaccine Group

Andrew J. Pollard

University of Oxford - Centre for Vaccinology and Tropical Medicine

RHH-001 Study Team

More...

Abstract

The inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, Sinovac) is one of the most widely used COVID-19 vaccines and is administered in a two-dose schedule. A third dose of the homologous or a different vaccine may boost waning immunity and provide improved protection particularly against new coronavirus variants.

Methods: We conducted a phase 4 randomised single-blind two-centre safety and immunogenicity study of a third heterologous booster dose of either the recombinant adenoviral-vectored ChAdOx1 nCoV-19 vaccine (AZD1222, AstraZeneca), an mRNA vaccine (BNT162b2, Pfizer/BioNTech), or a recombinant adenoviral vectored vaccine (AD26.COV2-S, Janssen), compared with a third homologous booster dose of CoronaVac in Brazilian adults who had received two doses of CoronaVac 6 months previously.

The primary outcome was non-inferiority of anti-spike IgG antibodies 28 days after the booster dose in the heterologous boost groups compared with homologous regimen. Secondary outcomes included neutralising antibody titres at day 28, local and systemic reactogenicity profiles, adverse events and serious adverse events.

Results: Between 16 August 2021 and 1 September 2021, 1240 participants were randomised in São Paulo and Salvador, of whom 1239 were vaccinated. 1205 returned for their Day 28 visit and were eligible for inclusion in the primary analysis. Antibody levels were low prior to administration of a booster dose with 20.4 % (CI) of adults aged 18-60 years and 8.9% (CI) of older adults (aged more than 60 years) having detectable neutralising antibodies.

At Day 28 after the booster vaccine all groups had a substantial rise in IgG antibody levels. The geometric fold-rise from baseline to day 28 was 90 (95%CI 77, 104) for ChAdOx1 nCoV-19, 12 (95%CI 11, 14) for CoronaVac, 77 (95%CI 67, 88) for AD26.COV2-S, and 152 (95%CI 134, 173) for BNT162b2.

All heterologous regimes had anti-spike IgG responses at Day 28 that were superior to homologous booster responses. Geometric mean ratios (heterologous vs homologous) were 7.0 (95%CI 6.1, 8.1) for ChAdOx1 nCoV-19, 6.7 (95% CI 5.8, 7.7) for AD26.COV2-S vaccine, and 13.4 (95% CI 11.6, 15.3) for BNT162b2.

All heterologous boost regimens induced high levels of pseudovirus neutralising antibodies with 100% seropositivity in all groups except for the homologous boost in older adults which achieved 66.7% seropositivity. Geometric mean ratios (heterologous vs homologous) were 10.6 (95%CI 7.2, 15.6) for ChAdOx1 nCoV-19, 8.7 (95% CI 5.9, 12.9) for AD26.COV2-S vaccine, and 21.5 (95% CI 14.5, 31.9) for BNT162b2.

Conclusion: Antibody responses were low at 6 months after prior immunisation with two doses of CoronaVac, However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibody, which may improve protection against infection.

Trial Regisration: Study registration: Registro Brasileiro de Ensaios Clínicos (RBR – 9nn3scw). REBEC (ensaiosclinicos.gov.br) - https://ensaiosclinicos.gov.br/rg/RBR-9nn3scw.

Funding: The study was funded by the Ministry of Health, Brazil, and sponsored by Instituto D’Or de Pesquisa e Ensino (IDOR). The investigators acknowledge, in-kind support from AstraZeneca for the serological assays presented in this manuscript.

Declaration of Interest: AJP is chair of the UK Department of Health and Social Care's Joint Committee on Vaccination and Immunisation, but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts (SAGE). AJP is an NIHR Senior Investigator. TL is named as an inventor on a patent application covering ChAdOx1 nCoV-19. Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. All other authors declare no competing interests.

Ethical Approval: Ethical approval was given by National Ethical Review Committee, Comissão Nacional de Ética em Pesquisa (CONEP).

Keywords: Randomized, Immunogenicity, Safety, study, heterologous, homologous, COVID-19, booster, vaccination, two dose, three dose, third, second, Coronavac, Sinovac, SARS-CoV-2, schedule, coronavirus, pandemic, Oxford, Brazil, Ministry of Health, protection

Suggested Citation

Costa Clemens, Sue Ann and Weckx, Lily Yin and Clemens, Ralf and Almeida Mendes, Ana Verena and Ramos Souza, Alessandra and Silveira, Mariana V. and Nascimento Farias da Guarda, Suzete and Miyamotode Nobrega, Maristela and de Moraes Pinto, Maria Isabel and Gonzalez, Isabela G. S. and Salvador, Natalia and Franco, Marilia Miranda and de Avila Mendonça, Renata Navis and Queiroz Oliveira, Isabelle Silva and de Freitas Souza, Bruno Solano and Fraga, Mayara and Aley, Parvinder K. and Bibi, Sagida and Cantrell, Liberty and Lambe, Teresa and Voysey, Merryn and Pollard, Andrew J. and Team, RHH-001 Study, Randomized Immunogenicity and Safety Study of Heterologous Versus Homologous COVID-19 Booster Vaccination in Previous Recipients of Two Doses Of Coronavac COVID-19 Vaccine. Available at SSRN: https://ssrn.com/abstract=3989848 or http://dx.doi.org/10.2139/ssrn.3989848

Sue Ann Costa Clemens

University of Siena - Institute of Global Health

Via Banchi di Sotto, 55
Siena, 53100
Italy

Lily Yin Weckx

Federal University of Sao Paulo ( email )

Ralf Clemens

affiliation not provided to SSRN ( email )

No Address Available

Ana Verena Almeida Mendes

affiliation not provided to SSRN ( email )

No Address Available

Alessandra Ramos Souza

affiliation not provided to SSRN ( email )

No Address Available

Mariana V. Silveira

affiliation not provided to SSRN ( email )

No Address Available

Suzete Nascimento Farias da Guarda

affiliation not provided to SSRN ( email )

No Address Available

Maristela Miyamotode Nobrega

affiliation not provided to SSRN ( email )

No Address Available

Maria Isabel De Moraes Pinto

affiliation not provided to SSRN ( email )

No Address Available

Isabela G. S. Gonzalez

affiliation not provided to SSRN ( email )

No Address Available

Natalia Salvador

affiliation not provided to SSRN ( email )

No Address Available

Marilia Miranda Franco

affiliation not provided to SSRN ( email )

No Address Available

Renata Navis De Avila Mendonça

affiliation not provided to SSRN ( email )

No Address Available

Isabelle Silva Queiroz Oliveira

affiliation not provided to SSRN ( email )

No Address Available

Bruno Solano De Freitas Souza

affiliation not provided to SSRN ( email )

No Address Available

Mayara Fraga

affiliation not provided to SSRN ( email )

No Address Available

Parvinder K. Aley

University of Oxford - Centre for Vaccinology and Tropical Medicine ( email )

Oxford
United Kingdom

Sagida Bibi

University of Oxford - Centre for Vaccinology and Tropical Medicine ( email )

Oxford
United Kingdom

Liberty Cantrell

University of Oxford ( email )

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Teresa Lambe

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Merryn Voysey

University of Oxford - Oxford Vaccine Group

Andrew J. Pollard (Contact Author)

University of Oxford - Centre for Vaccinology and Tropical Medicine ( email )

Oxford
United Kingdom

No contact information is available for RHH-001 Study Team

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