SCB-2019 protein vaccine as heterologous booster of neutralizing activity against SARS-CoV-2 Omicron variants after immunization with other COVID-19 vaccines

ABSTRACT

We assessed the non-inferiority of homologous boosting compared with heterologous boosting with the recombinant protein vaccine, SCB-2019, in adults previously immunized with different COVID-19 vaccines. Three equal cohorts (N ~ 420) of Philippino adults (18–80 years) previously immunized with Comirnaty, CoronaVac or Vaxzevria COVID-19 vaccines were randomized 1:1 to receive homologous or heterologous (SCB-2019) boosters. Neutralizing antibodies against prototype SARS-CoV-2 (Wuhan-Hu-1) were measured in all participants and against Delta variant and Omicron sub-lineages in subsets (30‒50 per arm) 15 days after boosting. Participants recorded solicited adverse events for 7 days and unsolicited and serious adverse events until Day 60. Prototype SARS-CoV-2 neutralizing responses on Day 15 after SCB-2019 were statistically non-inferior to homologous Vaxzevria boosters, superior to CoronaVac, but lower than homologous Comirnaty. Neutralizing responses against Delta and Omicron BA.1, BA.2, BA.4 and BA.5 variants after heterologous SCB-2019 were higher than homologous CoronaVac or Vaxzevria, but lower than homologous Comirnaty. Responses against Omicron BF.7, BQ.1.1.3, and XBB1.5 following heterologous SCB-2019 were lower than after homologous Comirnaty booster but significantly higher than after Vaxzevria booster. SCB-2019 reactogenicity was similar to CoronaVac or Vaxzevria, but lower than Comirnaty; most frequent events were mild/moderate injection site pain, headache and fatigue. No vaccine-related serious adverse events were reported. Heterologous SCB-2019 boosting was well tolerated and elicited neutralizing responses against all tested SARS-COV-2 viruses including Omicron BA.1, BA.2, BA.4, BA.5, BF.7, BQ.1.1.3, and XBB1.5 sub-lineages that were non-inferior to homologous boosting with CoronaVac or Vaxzevria, but not homologous Comirnaty booster.

KEYWORDS:

• Vaccine
• COVID-19
• heterologous booster
• homologous booster
• Comirnaty
• CoronaVac
• Vaxzevria
• SCB-2019
• Delta
• Omicron

Acknowledgments

We are grateful to all the participants who volunteered to be in this study, and to the staff at all the study centers for their invaluable support. Professors Sue Ann Costa Clemens and Emanuele Montomoli, and Drs. Peter Richmond and Anh Wartel are thanked for their expert advice and contributions. Editorial assistance in the preparation of this article was provided by Dr. Keith Veitch of KeithVeitch Communications (Amsterdam, the Netherlands) with the financial support of Clover Biopharmaceuticals.

Disclosure statement

Eric Plennevaux, Igor Smolenov, Branda Hu, Faith Gao, Hannalyn Ilagan and Htay Htay Han are full-time employees of the study sponsor. George Siber has served as a Scientific Advisory Board Member and received consulting fees from Clover Biopharmaceuticals, AdVaccine, CanSino, Everest Medicines, Valneva, Senda and Vaxart and owns equities in Clover, AdVaccine, Vaxxinity and Everest Medicines. Donna Ambrosino has received consulting fees from Clover Biopharmaceuticals, Vaxxinity, Everest Medicines, Senda, and served as a Scientific Advisory Board Member for Clover Biopharmaceuticals, Vaxxinity, Senda, Everest Medicines, and Inventprise, and served as a board member for Clover Biopharmaceuticals and Inventprise and owns stock in Clover, Everest Medicine, and Inventprise. Ralf Clemens has received funding from the Bill & Melinda Gates Foundation, consulting fees from Icosavax, Hillevax, honoraria from AstraZeneca, served as a board member for Clover Biopharmaceuticals, Curevac, IVI, Inventprise and owns stocks in Icosavax, HilleVax, Curevac, Novartis, Roche, GSK, and Clover Biopharmaceuticals. Camilo C. Roa, Jr. and Mari Rose A. de Los Reyes have no competing interests to declare.

Supplementary data

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2023.2301632.

Author contributions

Eric Plennevaux, Igor Smolenov, Branda Hu, Faith Gao, Hannalyn Ilagan contributed to the conception, design, and conduct of the study, analysis and interpretation of data and drafting the article. Camilo C. Roa, Jr., Mari Rose A. de Los Reyes contributed to the acquisition of data and revising the article. Htay Htay Han, Donna Ambrosino, George Siber, and Ralf Clemens participated in the analysis and interpretation of data and revision of the article. All authors gave their final approval of the version to be submitted.

Additional information

Funding

Sponsorship for this study was entirely funded by Clover Biopharmaceuticals.