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

Clemens, Sue Ann Costa; Weckx, Lily Yin; Clemens, Ralf; Mendes, Ana Verena Almeida; Souza, Alessandra R.; Silveira, Mariana Vela; Guarda, Suzete Nascimento Farias da; Nobrega, Maristela Miyamotode; Pinto, Mariana Tomazini; Gonzalez, Isabela G. S.; Salvador, Natalia Zerbinatti; Franco, Marília Miranda; Mendonça, Renata Navis de Avila; Oliveira, Isabelle Silva Queiroz; Souza, Bruno Solano de Freitas; Fraga, Mayara; Aley, Parvinder K.; Bibi, Sagida; Cantrell, Liberty; Lambe, Teresa; Voysey, Merryn; Pollard, Andrew J.

doi:10.2139/ssrn.3989848

Cited by 17 publications

(22 citation statements)

References 6 publications

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“…Interestingly, without sacrificing potency against Delta, heterologous Omicron booster achieved significantly higher neutralizing titers against Omicron than homologous WT booster. This observation is in line with findings from heterologous booster vaccination of different COVID-19 vaccines in clinical trials 25,26 . The broad anti-coronavirus activity after homologous or heterologous boosting was likely associated with plasma antibodies in rarer epitope classes, as observed in competition ELISA.…”

Section: Discussionsupporting

confidence: 89%

Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2

Fang

Peng

Lin

et al. 2022

Preprint

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The Omicron variant of SARS-CoV-2 has high transmissibility and recently been sweeping the globe, dominating new infection cases in the US and many regions in the world. Due to its extensive number of mutations, this variant has high level of immune evasion, which drastically reduced the efficacy of existing antibodies and vaccines. Thus, it is important to develop an Omicron-specific vaccine and test if it can induce immune responses against Omicron and broadly against other variants. Here, we generated an Omicron-specific lipid nanoparticle (LNP) mRNA vaccine candidate, and tested its potency of antibody induction in animals, both alone and as a booster to existing mRNA vaccine designed against the ancestral reference virus (WA-1). This Omicron-specific LNP-mRNA vaccine elicited strong and specific antibody response in vaccination-naïve mice. Consistent with recent reports, mice that received two-dose WA-1 LNP-mRNA, the one mimicking the commonly used Pfizer/Moderna mRNA vaccine administered in the general population, showed a 41-fold reduction in neutralization potency against Omicron variant as compared to WA-1 two weeks post second dose, which further reduced to background level 3.5 months post second dose. As a booster for WA-1 mRNA vaccination, a single dose Omicron LNP-mRNA induced potent antibody response against the Omicron variant, with over 1,000-fold increase at two weeks post injection as compared to the blood samples right before booster. The Omicron-specific antibody level of the Omicron-boosted samples is numerically similar to WA-1 vaccine against WA-1 variant. This boost also elicited broader antibody responses against WA-1 and Delta variants, restoring these activities of the WA-1 vaccinated animals that also dropped over time. A consecutive second dose of Omicron LNP-mRNA 2 weeks following the first dose did not significantly increased the level of antibodies. These in vivo animal data provided a timely proof-of-concept for Omicron-specific mRNA vaccination, alone and as a booster to the existing widely-used mRNA vaccine form.

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Section: Discussionsupporting

confidence: 89%

Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2

Fang

Peng

Lin

et al. 2022

Preprint

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“…It is increasingly evident that three doses of COVID-19 vaccines with homologous mRNA schedule or heterologous schedule with mRNA as booster are needed to protect against the Omicron variant 26,27 . This is in line with recent immunological studies that showed that three doses of homologous mRNA schedule or heterologous schedule with mRNA as booster induced high levels of neutralising antibodies against Delta and Omicron variants [28][29][30] .…”

Section: (Which Was Not Certified By Peer Review)supporting

confidence: 89%

Immunogenicity and reactogenicity against the SARS-CoV-2 variants following heterologous primary series involving CoronaVac and ChAdOx1 and BNT162b2 plus heterologous BNT162b2 booster vaccination: An open-label randomized study in healthy Thai adults

Niyomnaitham

Toh

Wongprompitak

et al. 2022

Preprint

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We evaluated the immunogenicity and reactogenicity of heterologous COVID-19 primary series vaccination schedules. Participants were randomized to one of seven groups that received two-dose homologous BNT162b2 or heterologous combinations of CoronaVac, ChAdOx1 and BNT162b2, with 4 weeks interval. Of 210 participants, median age was 38 (19-60) years, 51% were female. The groups that received BNT162b2 as second dose induced the highest virus-specific IgG response against the ancestral strain [BNT162b2: geometric mean concentration (GMC) 2133-2249, 95%CI 1558 to 3055; ChAdOx1: 851-1201, 95%CI 649 to 1522; CoronaVac: 137-225, 95%CI 103-286 BAU/mL], neutralising antibodies (NAb) against Beta and Delta, and interferon gamma response. All groups induced low to negligible NAb against Omicron. A BNT162b2 booster (3rd dose) following heterologous CoronaVac and ChAdOx1 regimens induced >140-fold increase in NAb titres against Omicron. Our findings indicate that heterologous regimens using BNT162b2 as the second dose may be considered an alternative schedule to maximize immune response.

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“…Booster vaccination strategies based on inactivated vaccine priming have been well studied, and heterologous vaccination regimens induce immune responses that are superior to those induced by homologous regimens (9)(10)(11)(12). Clemens et al reported that the increases in specific IgG titers from baseline to 28 days were 12-fold for CoronaVac (the inactivated vaccine), 152-fold for BNT162b2, 90-fold for ChAdOx1 nCoV-19, and 77-fold for Ad26.COV2.S after booster vaccination in CoronaVac-primed recipients (11).…”

Section: Introductionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted March 10, 2022. ; https://doi.org /10.1101/10. /2022 CoronaVac-primed recipients (11). Li et al reported that neutralizing antibody titers were increased by 79-fold for Ad5-nCoV booster vaccination and by 15-fold for CoronaVac booster vaccination from before booster vaccination to day 14 after booster vaccination in subjects who received two doses of CoronaVac (12).…”

Section: Introductionmentioning

confidence: 99%

Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming

Zhang¹,

Wu²,

Liu

et al. 2022

Preprint

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The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant around the world and exhibits immune escape to current COVID-19 vaccines to some extent due to its numerous spike mutations. Here, we evaluated the immune responses to booster vaccination with intramuscular adenovirus-vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines 6 months prior. We found that the Ad5-nCoV booster induced potent neutralizing activity against the wild-type virus and Omicron variant, while aerosolized Ad5-nCoV generated the greatest neutralizing antibody responses against the Omicron variant at day 28 after booster vaccination, at 14.1-fold that of CoronaVac, 5.6-fold that of ZF2001 and 2.0-fold that of intramuscular Ad5-nCoV. Similarly, the aerosolized Ad5-nCoV booster produced the greatest IFNgamma T-cell response at day 14 after booster vaccination. The IFNgamma T-cell response to aerosolized Ad5-nCoV was 12.8-fold for CoronaVac, 16.5-fold for ZF2001, and 5.0-fold for intramuscular Ad5-nCoV. Aerosolized Ad5-nCoV booster also produced the greatest spike-specific B cell response. Our findings suggest that inactivated vaccine recipients should consider adenovirus-vectored vaccine boosters in China and that aerosolized Ad5-nCoV may provide a more efficient alternative in response to the spread of the Omicron variant.

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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

Cited by 17 publications

References 6 publications

Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2

Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2

Immunogenicity and reactogenicity against the SARS-CoV-2 variants following heterologous primary series involving CoronaVac and ChAdOx1 and BNT162b2 plus heterologous BNT162b2 booster vaccination: An open-label randomized study in healthy Thai adults

Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming

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