Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine

Dayan, Gustavo H.; Rouphael, Nadine; Walsh, Stephen R.; Chen, Aiying; Grunenberg, Nicole; Allen, Mary; Antony, Johannes; Asante, Kwaku Poku; Bhate, Amit Suresh; Beresnev, Tatiana; Bonaparte, Matthew; Ceregido, Maria Angeles; Dobrianskyi, Dmytro; Fu, Bo; Grillet, Marie-Hélène; Keshtkar-Jahromi, Maryam; Juraska, Michal; Kee, Jia Jin; Kibuuka, Hannah; Koutsoukos, Marguerite; Masotti, Roger; Michael, Nelson L.; Reynales, Humberto; Robb, Merlin L.; Martínez, Sandra M. Villagómez; Sawe, Fredrick; Schuerman, Lode; Tong, Tina; Treanor, John J.; Wartel, T. Anh; DiazGranados, Carlos A.; Chicz, Roman M.; Gurunathan, Sanjay; Savarino, Stephen J.; Sridhar, Saranya

doi:10.1101/2022.12.05.22282933

Cited by 10 publications

(16 citation statements)

References 35 publications

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“…These data provide information about alternative boosting strategies to address the risks associated with SARS-CoV-2 VOCs and waning immunity. Based on these encouraging results, Betacontaining vaccine formulations are being evaluated as booster vaccines in a clinical trial, and preliminary results confirm and extend our observations in primed NHPs by showing a superiority of the Betacontaining vaccine when compared to the ancestral D614 vaccine for the neutralization of a wide range of variants (NCT04762680, NCT04904549, and NCT05124171) [8][9][10] .…”

Section: Discussionsupporting

confidence: 71%

“…These observations have been confirmed in two Phase 3 clinical trials (NCT04762680 and NCT05124171), demonstrating that our Beta-containing booster vaccine candidate delivered a strong immune response against VOCs, including Omicron, in adults primed with mRNA vaccines and conferred strong efficacy against symptomatic infection in adults and participants previously infected with SARS-CoV-2 3,[8][9][10] .…”

supporting

confidence: 55%

“…The potent and prolonged booster effect up to 6 months against VOCs provided by a booster dose with the Beta-containing recombinant CoV2 preS dTM-AS03 vaccine candidate in NHPs, combined with the encouraging results from clinical trials presents unique benefits for future booster vaccination campaigns 3,[8][9][10] .…”

mentioning

confidence: 99%

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Beta variant COVID-19 protein booster vaccine elicits durable cross-neutralization against SARS-CoV-2 variants in non-human primates

et al. 2023

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The rapid spread of the SARS-CoV-2 Omicron subvariants, despite the implementation of booster vaccination, has raised questions about the durability of protection conferred by current vaccines. Vaccine boosters that can induce broader and more durable immune responses against SARS-CoV-2 are urgently needed. We recently reported that our Beta-containing protein-based SARS-CoV-2 spike booster vaccine candidates with AS03 adjuvant (CoV2 preS dTM-AS03) elicited robust cross-neutralizing antibody responses at early timepoints against SARS-CoV-2 variants of concern in macaques primed with mRNA or protein-based subunit vaccine candidates. Here we demonstrate that the monovalent Beta vaccine with AS03 adjuvant induces durable cross-neutralizing antibody responses against the prototype strain D614G as well as variants Delta (B.1.617.2), Omicron (BA.1 and BA.4/5) and SARS-CoV-1, that are still detectable in all macaques 6 months post-booster. We also describe the induction of consistent and robust memory B cell responses, independent of the levels measured post-primary immunization. These data suggest that a booster dose with a monovalent Beta CoV2 preS dTM-AS03 vaccine can induce robust and durable cross-neutralizing responses against a broad spectrum of variants.

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Section: Discussionsupporting

confidence: 71%

supporting

confidence: 55%

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Beta variant COVID-19 protein booster vaccine elicits durable cross-neutralization against SARS-CoV-2 variants in non-human primates

et al. 2023

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“…Due to various concerns, including the longevity of protection and the association of adenovirus and mRNA-based vaccines with rare, but serious side effects, different vaccine platforms are still being actively evaluated to produce new vaccines to target SARS-CoV-2 variants (22). For example, a few protein subunit variantbased vaccine formulations have also been assessed clinically in the context of a booster dose (23)(24)(25). Also, bivalent or multivalent protein vaccine formulations have been used to both prime and boost immune responses within a preclinical setting, resulting in an increased breadth of the neutralization response (16,26).…”

Section: Neutralizing Activitymentioning

confidence: 99%

Tuning the immune response: sulfated archaeal glycolipid archaeosomes as an effective vaccine adjuvant for induction of humoral and cell-mediated immunity towards the SARS-CoV-2 Omicron variant of concern

et al. 2023

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Liposomes composed of sulfated lactosyl archaeol (SLA) have been shown to be a safe and effective vaccine adjuvant with a multitude of antigens in preclinical studies. In particular, SLA-adjuvanted SARS-CoV-2 subunit vaccines based on trimeric spike protein antigens were shown to be immunogenic and efficacious in mice and hamsters. With the continued emergence of SARS-CoV-2 variants, we sought to evaluate next-generation vaccine formulations with an updated antigenic identity. This was of particular interest for the widespread Omicron variant, given the abundance of mutations and structural changes observed within its spike protein compared to other variants. An updated version of our resistin-trimerized SmT1 corresponding to the B.1.1.529 variant was successfully generated in our Chinese Hamster Ovary (CHO) cell-based antigen production platform and characterized, revealing some differences in protein profile and ACE2 binding affinity as compared to reference strain-based SmT1. We next evaluated this Omicron-based spike antigen for its immunogenicity and ability to generate robust antigen-specific immune responses when paired with SLA liposomes or AddaS03 (a mimetic of the AS03 oil-in-water emulsion adjuvant system found in commercialized SARS-CoV-2 protein vaccines). Immunization of mice with vaccine formulations containing this updated antigen with either adjuvant stimulated neutralizing antibody responses favouring Omicron over the reference strain. Cell-mediated responses, which play an important role in the neutralization of intracellular infections, were induced to a much higher degree with the SLA adjuvant relative to the AddaS03-adjuvanted formulations. As such, updated vaccines that are better capable of targeting towards SARS-CoV-2 variants can be generated through an optimized combination of antigen and adjuvant components.

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“…The PREVENT-19 (Prefusion Protein Subunit Vaccine Efficacy Novavax TRIAL COVID-19) study (Novavax)20 had a dosing interval of 2 doses of NVX-CoV2373 21 days apart, measuring efficacy from 7 days after the second dose. The VAT0008 study (Sanofi Pasteur)21…”

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confidence: 99%

Rapid Development of an Integrated Network Infrastructure to Conduct Phase 3 COVID-19 Vaccine Trials

et al. 2023

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ImportanceThe COVID-19 pandemic has caused millions of infections and deaths and resulted in unprecedented international public health social and economic crises. As SARS-CoV-2 spread across the globe and its impact became evident, the development of safe and effective vaccines became a priority. Outlining the processes used to establish and support the conduct of the phase 3 randomized clinical trials that led to the rapid emergency use authorization and approval of several COVID-19 vaccines is of major significance for current and future pandemic response efforts.ObservationsTo support the rapid development of vaccines for the US population and the rest of the world, the National Institute of Allergy and Infectious Diseases established the COVID-19 Prevention Network (CoVPN) to assist in the coordination and implementation of phase 3 efficacy trials for COVID-19 vaccine candidates and monoclonal antibodies. By bringing together multiple networks, CoVPN was able to draw on existing clinical and laboratory infrastructure, community partnerships, and research expertise to quickly pivot clinical trial sites to conduct COVID-19 vaccine trials as soon as the investigational products were ready for phase 3 testing. The mission of CoVPN was to operationalize phase 3 vaccine trials using harmonized protocols, laboratory assays, and a single data and safety monitoring board to oversee the various studies. These trials, while staggered in time of initiation, overlapped in time and course of conduct and ultimately led to the successful completion of multiple studies and US Food and Drug Administration–licensed or –authorized vaccines, the first of which was available to the public less than 1 year from the discovery of the virus.Conclusions and RelevanceThis Special Communication describes the design, geographic distribution, and underlying principles of conduct of these efficacy trials and summarizes data from 136 382 prospectively followed-up participants, including more than 2500 with documented COVID-19. These successful efforts can be replicated for other important research initiatives and point to the importance of investments in clinical trial infrastructure integral to pandemic preparedness.

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Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine

Cited by 10 publications

References 35 publications

Beta variant COVID-19 protein booster vaccine elicits durable cross-neutralization against SARS-CoV-2 variants in non-human primates

Beta variant COVID-19 protein booster vaccine elicits durable cross-neutralization against SARS-CoV-2 variants in non-human primates

Tuning the immune response: sulfated archaeal glycolipid archaeosomes as an effective vaccine adjuvant for induction of humoral and cell-mediated immunity towards the SARS-CoV-2 Omicron variant of concern

Rapid Development of an Integrated Network Infrastructure to Conduct Phase 3 COVID-19 Vaccine Trials

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