tetano
Editor, Senior Moderator
Nat Med
. 2023 Aug 28.
doi: 10.1038/s41591-023-02503-4. Online ahead of print. Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial
Angela R Branche[SUP] #[/SUP][SUP] 1 [/SUP], Nadine G Rouphael[SUP] #[/SUP][SUP] 2 [/SUP], David J Diemert[SUP] 3 [/SUP], Ann R Falsey[SUP] 4 [/SUP], Cecilia Losada[SUP] 2 [/SUP], Lindsey R Baden[SUP] 5 [/SUP], Sharon E Frey[SUP] 6 [/SUP], Jennifer A Whitaker[SUP] 7 [/SUP], Susan J Little[SUP] 8 [/SUP], Evan J Anderson[SUP] 9 [/SUP], Emmanuel B Walter[SUP] 10 [/SUP], Richard M Novak[SUP] 11 [/SUP], Richard Rupp[SUP] 12 [/SUP], Lisa A Jackson[SUP] 13 [/SUP], Tara M Babu[SUP] 14 [/SUP], Angelica C Kottkamp[SUP] 15 [/SUP], Anne F Luetkemeyer[SUP] 16 [/SUP], Lilly C Immergluck[SUP] 17 [/SUP], Rachel M Presti[SUP] 18 [/SUP], Martín Bäcker[SUP] 19 [/SUP], Patricia L Winokur[SUP] 20 [/SUP], Siham M Mahgoub[SUP] 21 [/SUP], Paul A Goepfert[SUP] 22 [/SUP], Dahlene N Fusco[SUP] 23 [/SUP], Elissa Malkin[SUP] 3 [/SUP], Jeffrey M Bethony[SUP] 3 [/SUP], Edward E Walsh[SUP] 4 [/SUP], Daniel S Graciaa[SUP] 2 [/SUP], Hady Samaha[SUP] 2 [/SUP], Amy C Sherman[SUP] 5 [/SUP], Stephen R Walsh[SUP] 5 [/SUP], Getahun Abate[SUP] 6 [/SUP], Zacharoula Oikonomopoulou[SUP] 6 [/SUP], Hana M El Sahly[SUP] 7 [/SUP], Thomas C S Martin[SUP] 8 [/SUP], Satoshi Kamidani[SUP] 9 [/SUP], Michael J Smith[SUP] 10 [/SUP], Benjamin G Ladner[SUP] 11 [/SUP], Laura Porterfield[SUP] 12 [/SUP], Maya Dunstan[SUP] 13 [/SUP], Anna Wald[SUP] 14 [/SUP], Tamia Davis[SUP] 15 [/SUP], Robert L Atmar[SUP] 7 [/SUP], Mark J Mulligan[SUP] 15 [/SUP], Kirsten E Lyke[SUP] 24 [/SUP], Christine M Posavad[SUP] 25 [/SUP], Megan A Meagher[SUP] 25 [/SUP], David S Stephens[SUP] 26 [/SUP], Kathleen M Neuzil[SUP] 24 [/SUP], Kuleni Abebe[SUP] 27 [/SUP], Heather Hill[SUP] 28 [/SUP], Jim Albert[SUP] 29 [/SUP], Kalyani Telu[SUP] 29 [/SUP], Jinjian Mu[SUP] 29 [/SUP], Teri C Lewis[SUP] 30 [/SUP], Lisa A Giebeig[SUP] 30 [/SUP], Amanda Eaton[SUP] 10 28 [/SUP], Antonia Netzl[SUP] 31 [/SUP], Samuel H Wilks[SUP] 31 [/SUP], Sina Türeli[SUP] 31 [/SUP], Mamodikoe Makhene[SUP] 32 [/SUP], Sonja Crandon[SUP] 32 [/SUP], David C Montefiori[SUP] 10 28 [/SUP], Mat Makowski[SUP] 29 [/SUP], Derek J Smith[SUP] 31 [/SUP], Seema U Nayak[SUP] 32 [/SUP], Paul C Roberts[SUP] #[/SUP][SUP] 32 [/SUP], John H Beigel[SUP] #[/SUP][SUP] 32 [/SUP]; COVAIL Study Group
Collaborators, Affiliations
Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID[SUB]50[/SUB] titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID[SUB]50[/SUB] titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 .
. 2023 Aug 28.
doi: 10.1038/s41591-023-02503-4. Online ahead of print. Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial
Angela R Branche[SUP] #[/SUP][SUP] 1 [/SUP], Nadine G Rouphael[SUP] #[/SUP][SUP] 2 [/SUP], David J Diemert[SUP] 3 [/SUP], Ann R Falsey[SUP] 4 [/SUP], Cecilia Losada[SUP] 2 [/SUP], Lindsey R Baden[SUP] 5 [/SUP], Sharon E Frey[SUP] 6 [/SUP], Jennifer A Whitaker[SUP] 7 [/SUP], Susan J Little[SUP] 8 [/SUP], Evan J Anderson[SUP] 9 [/SUP], Emmanuel B Walter[SUP] 10 [/SUP], Richard M Novak[SUP] 11 [/SUP], Richard Rupp[SUP] 12 [/SUP], Lisa A Jackson[SUP] 13 [/SUP], Tara M Babu[SUP] 14 [/SUP], Angelica C Kottkamp[SUP] 15 [/SUP], Anne F Luetkemeyer[SUP] 16 [/SUP], Lilly C Immergluck[SUP] 17 [/SUP], Rachel M Presti[SUP] 18 [/SUP], Martín Bäcker[SUP] 19 [/SUP], Patricia L Winokur[SUP] 20 [/SUP], Siham M Mahgoub[SUP] 21 [/SUP], Paul A Goepfert[SUP] 22 [/SUP], Dahlene N Fusco[SUP] 23 [/SUP], Elissa Malkin[SUP] 3 [/SUP], Jeffrey M Bethony[SUP] 3 [/SUP], Edward E Walsh[SUP] 4 [/SUP], Daniel S Graciaa[SUP] 2 [/SUP], Hady Samaha[SUP] 2 [/SUP], Amy C Sherman[SUP] 5 [/SUP], Stephen R Walsh[SUP] 5 [/SUP], Getahun Abate[SUP] 6 [/SUP], Zacharoula Oikonomopoulou[SUP] 6 [/SUP], Hana M El Sahly[SUP] 7 [/SUP], Thomas C S Martin[SUP] 8 [/SUP], Satoshi Kamidani[SUP] 9 [/SUP], Michael J Smith[SUP] 10 [/SUP], Benjamin G Ladner[SUP] 11 [/SUP], Laura Porterfield[SUP] 12 [/SUP], Maya Dunstan[SUP] 13 [/SUP], Anna Wald[SUP] 14 [/SUP], Tamia Davis[SUP] 15 [/SUP], Robert L Atmar[SUP] 7 [/SUP], Mark J Mulligan[SUP] 15 [/SUP], Kirsten E Lyke[SUP] 24 [/SUP], Christine M Posavad[SUP] 25 [/SUP], Megan A Meagher[SUP] 25 [/SUP], David S Stephens[SUP] 26 [/SUP], Kathleen M Neuzil[SUP] 24 [/SUP], Kuleni Abebe[SUP] 27 [/SUP], Heather Hill[SUP] 28 [/SUP], Jim Albert[SUP] 29 [/SUP], Kalyani Telu[SUP] 29 [/SUP], Jinjian Mu[SUP] 29 [/SUP], Teri C Lewis[SUP] 30 [/SUP], Lisa A Giebeig[SUP] 30 [/SUP], Amanda Eaton[SUP] 10 28 [/SUP], Antonia Netzl[SUP] 31 [/SUP], Samuel H Wilks[SUP] 31 [/SUP], Sina Türeli[SUP] 31 [/SUP], Mamodikoe Makhene[SUP] 32 [/SUP], Sonja Crandon[SUP] 32 [/SUP], David C Montefiori[SUP] 10 28 [/SUP], Mat Makowski[SUP] 29 [/SUP], Derek J Smith[SUP] 31 [/SUP], Seema U Nayak[SUP] 32 [/SUP], Paul C Roberts[SUP] #[/SUP][SUP] 32 [/SUP], John H Beigel[SUP] #[/SUP][SUP] 32 [/SUP]; COVAIL Study Group
Collaborators, Affiliations
- PMID: 37640860
- DOI: 10.1038/s41591-023-02503-4
Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID[SUB]50[/SUB] titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID[SUB]50[/SUB] titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 .