Safety and immunogenicity of a variant-adapted SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant as a booster in adults primed with authorized vaccines: a phase 3, parallel-group study

Bruyn, Guy de; Wang, Joyce; Purvis, Annie; Ruiz, Martin Sanchez; Adhikarla, Haritha; Alvi, Saad; Bonaparte, Matthew; Brune, Daniel C.; Bueso, Agustin; Canter, Richard; Ceregido, Maria Angeles; Deshmukh, Sachin Kumar; Diemert, David; Finn, Adam; Forrat, Rémi; Fu, Bo; Gallais, Julie; Griffin, Paul; Grillet, Marie-Hélène; Haney, Owen; Henderson, Jeffrey A.; Koutsoukos, Marguerite; Launay, Odile; Martinón-Torres, Federico; Masotti, Roger; Michael, Nelson L.; Park, Juliana; Rivera-Medina, Doris Maribel; Romanyak, Natalya; Rook, Chris; Schuerman, Lode; Sher, Lawrence; Silva, Fernanda Tavares Da; Whittington, Ashley; Chicz, Roman M.; Gurunathan, Sanjay; Savarino, Stephen J.; Sridhar, Saranya; Mohammed, Alaa Hamid; Boivin, Valérie; Do, Jennifer B.; Ben-Ghezala, Ines; Breuer, Thomas; Breymeier, Corinne; Conrad, Anne; Holmqvist, Catarina; Costa-Araujo, Cristiana; Coux, Florence; Dellanno, Christine; Dussol, Bertrand; Essink, Brandon; Garrido, Jesús; Girodet, Pierre‐Olivier; Gonzalez, Claudia; Grosbois, Marie-Ange; Hammond, Justin; He, Cui; Homlqvist, Ciarrah; Hudzina, Kathy; Hutchens, Mark; Booth, Peta-Gay Jackson; Joaquin, Arnel; Kandasamy, Rama; Kasztejna, Jennifer; Keefer, Michael C.; Kimmel, Murray; Kresge, M. Nicole; Lainé, Fabrice; Lefèbvre, M.; Lopez, Denise; Lourdes, M.; Maakaroun-Vermesse, Zoha; Malishchak, Caitlin; Menard, Laura; Mendoza, Sandra; Moore, Patrick; Mulamalla, Mounika; Mulholland, Patrick J.; Nicolas, Jean‐François; Ogbuagu, Onyema; Ortiz, Juan; Perroud, Ana Paula; Peyton, Gaylon A.; Purvis, Ya-Fen; Raabe, Vanessa; Rivas, Enrique; Rouphael, Nadine; Roy, Béatrice; Sagot, L.; Sater, Nessryne; Schwartz, Howard; Severance, Randall; Shi, Jiayuan; Sobieszczyk, Magdalena E.; Stevens, Cladd E.; Thuy, Tran Phuong; Toma, Radu Valeriu; Tong, Tina; Tourneux, Sophie; Treanor, John J.; Turet, Núria; Froget, Rachel; Walsh, Stephen R.; White, Judith M.; Pérez, Victor Del Campo; Breva, Lina Perez; Conejo, Pablo Rojo; Antoraz, Maria Belen Ruiz; Chin, Taylor; Fribbens, Charlotte; Phillipson, Adrian; Kaminski, R.M.; Emmett, Stevan R.; Hebert, Corey; Birch, Thomas; Roberson, Russell S.; Zacher, Jeffrey; Gelu-Maury, Sophie; Loryne, Loron; Davis, Yvonne

doi:10.1016/j.eclinm.2023.102109

Cited by 10 publications

(11 citation statements)

References 20 publications

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“…We next assessed neutralizing antibodies to Delta, Omicron BA.1, BA.2, and BA.4/5 in individuals from the Phase III booster cohorts [ 5 ]. Three formulations of the CoV2 preS dTM booster were each administered 4–10 months following primary vaccination with mRNA (Pfizer/BioNTech and Moderna) or adenoviral-vectored (AstraZeneca and Janssen) vaccines.…”

Section: Resultsmentioning

confidence: 99%

“…The original COVID-19 vaccines developed with the Spike antigen from the prototype Wuhan-1 strain provide short-term protection against infection [ 2 , 3 ], but little is known about elicitation of cross-neutralizing antibodies and consequent protection against Omicron with variant-based booster vaccines. Here, we measured cross-reactive serum-neutralizing responses to Delta, the variants of Omicron, including BA.1, BA.2, and BA.4/5 in participants from a clinical trial (NCT04762680) [ 4 , 5 ] assessing the primary series and booster of different recombinant pre-fusion stabilized, transmembrane domain-deleted Spike antigen-based (CoV2 preS dTM) vaccine candidates formulated incorporating the AS03-adjuvant with the live virus S-Fuse neutralization and lentivirus based pseudoneutralization assays [ [6] , [7] , [8] , [9] , [10] ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Beta-variant recombinant booster vaccine elicits broad cross-reactive neutralization of SARS-CoV-2 including Omicron variants

Planas,

Peng,

Zheng

et al. 2024

Heliyon

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Beta-variant recombinant booster vaccine elicits broad cross-reactive neutralization of SARS-CoV-2 including Omicron variants

Planas,

Peng,

Zheng

et al. 2024

Heliyon

Self Cite

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“…Here we demonstrate the Beta spike trimer in the Sanofi COVID booster vaccine has a preferential two RBD up conformation, providing twice the surface area of exposed RBD amino acids compared to the ancestral spike trimer booster vaccine. Three key mutations in the Beta spike RBD (K417N, E484A, and N501Y) are the target for two thirds of the most potent neutralizing antibodies identified from Beta SARS-CoV-2 infected individuals 32 , thus contributing to the broadly cross neutralizing immunogenicity demonstrated in the clinical development of the vaccine 12 , 13 and the real-world effectiveness against Omicron XBB.1.5 33 .…”

Section: Discussionmentioning

confidence: 99%

“…As the pandemic continued, the general population became progressively more exposed to circulating VOC and booster vaccine development became the priority. The monovalent Beta booster vaccine has demonstrated superior cross-neutralizing antibody titres and durability for up to one year in both preclinical NHP studies 10 , 11 and Phase 2/3 clinical trials comparing first generation ancestral strain mRNA and recombinant protein booster vaccines 12 , 13 .…”

Section: Introductionmentioning

confidence: 99%

Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2

Bruch,

Zhu,

Szymkowicz

et al. 2024

Sci Rep

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, uses a surface expressed trimeric spike glycoprotein for cell entry. This trimer is the primary target for neutralizing antibodies making it a key candidate for vaccine development. During the global pandemic circulating variants of concern (VOC) caused several waves of infection, severe disease, and death. The reduced efficacy of the ancestral trimer-based vaccines against emerging VOC led to the need for booster vaccines. Here we present a detailed characterization of the Sanofi Beta trimer, utilizing cryo-EM for structural elucidation. We investigate the conformational dynamics and stabilizing features using orthogonal SPR, SEC, nanoDSF, and HDX-MS techniques to better understand how this antigen elicits superior broad neutralizing antibodies as a variant booster vaccine. This structural analysis confirms the Beta trimer preference for canonical quaternary structure with two RBD in the up position and the reversible equilibrium between the canonical spike and open trimer conformations. Moreover, this report provides a better understanding of structural differences between spike antigens contributing to differential vaccine efficacy.

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“…For example, the efficacy of the whole-virus vaccine VLA2001 against the delta and omicron variants was improved after both homologous and ChAdOx1 nCoV-19 heterologous booster immunizations [ 174 ]. In another study, it was demonstrated that individuals originally vaccinated with mRNA or Ad-based vaccines, who received a booster immunization with the preS dTM-AS03 protein subunit vaccine carrying the beta variant S protein, showed robust neutralizing antibody responses against several SARS-CoV-2 VoC [ 38 ].…”

Section: Sars-cov-2 Variants and Vaccine Efficacymentioning

confidence: 99%

COVID-19 Vaccines: Where Did We Stand at the End of 2023?

Lundstrom

2024

Viruses

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Vaccine development against SARS-CoV-2 has been highly successful in slowing down the COVID-19 pandemic. A wide spectrum of approaches including vaccines based on whole viruses, protein subunits and peptides, viral vectors, and nucleic acids has been developed in parallel. For all types of COVID-19 vaccines, good safety and efficacy have been obtained in both preclinical animal studies and in clinical trials in humans. Moreover, emergency use authorization has been granted for the major types of COVID-19 vaccines. Although high safety has been demonstrated, rare cases of severe adverse events have been detected after global mass vaccinations. Emerging SARS-CoV-2 variants possessing enhanced infectivity have affected vaccine protection efficacy requiring re-design and re-engineering of novel COVID-19 vaccine candidates. Furthermore, insight is given into preparedness against emerging SARS-CoV-2 variants.

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Safety and immunogenicity of a variant-adapted SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant as a booster in adults primed with authorized vaccines: a phase 3, parallel-group study

Cited by 10 publications

References 20 publications

Beta-variant recombinant booster vaccine elicits broad cross-reactive neutralization of SARS-CoV-2 including Omicron variants

Beta-variant recombinant booster vaccine elicits broad cross-reactive neutralization of SARS-CoV-2 including Omicron variants

Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2

COVID-19 Vaccines: Where Did We Stand at the End of 2023?

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