tetano
Editor, Senior Moderator
Nat Commun
. 2025 Jan 17;16(1):759.
doi: 10.1038/s41467-025-55931-w. Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost
Bo Zhang[SUP] 1 [/SUP], Youyi Fong[SUP] 1 2 3 [/SUP], Lauren Dang[SUP] 4 [/SUP], Jonathan Fintzi[SUP] 4 [/SUP], Shiyu Chen[SUP] 1 [/SUP], Jing Wang[SUP] 5 [/SUP], Nadine G Rouphael[SUP] 6 [/SUP], Angela R Branche[SUP] 7 [/SUP], David J Diemert[SUP] 8 [/SUP], Ann R Falsey[SUP] 7 [/SUP], Daniel S Graciaa[SUP] 6 [/SUP], Lindsey R Baden[SUP] 9 [/SUP], Sharon E Frey[SUP] 10 [/SUP], Jennifer A Whitaker[SUP] 11 [/SUP], Susan J Little[SUP] 12 [/SUP], Satoshi Kamidani[SUP] 13 14 [/SUP], Emmanuel B Walter[SUP] 15 [/SUP], Richard M Novak[SUP] 16 [/SUP], Richard Rupp[SUP] 17 [/SUP], Lisa A Jackson[SUP] 18 [/SUP], Chenchen Yu[SUP] 1 [/SUP], Craig A Magaret[SUP] 1 [/SUP], Cindy Molitor[SUP] 1 [/SUP], Bhavesh Borate[SUP] 1 [/SUP], Sydney Busch[SUP] 19 [/SUP], David Benkeser[SUP] 19 [/SUP], Antonia Netzl[SUP] 20 [/SUP], Derek J Smith[SUP] 20 [/SUP], Tara M Babu[SUP] 21 [/SUP], Angelica C Kottkamp[SUP] 22 [/SUP], Anne F Luetkemeyer[SUP] 23 [/SUP], Lilly C Immergluck[SUP] 24 25 [/SUP], Rachel M Presti[SUP] 26 [/SUP], Martín Bäcker[SUP] 27 [/SUP], Patricia L Winokur[SUP] 28 [/SUP], Siham M Mahgoub[SUP] 29 [/SUP], Paul A Goepfert[SUP] 30 [/SUP], Dahlene N Fusco[SUP] 31 [/SUP], Robert L Atmar[SUP] 11 [/SUP], Christine M Posavad[SUP] 32 33 [/SUP], Jinjian Mu[SUP] 34 [/SUP], Mat Makowski[SUP] 34 [/SUP], Mamodikoe K Makhene[SUP] 35 [/SUP], Seema U Nayak[SUP] 35 [/SUP], Paul C Roberts[SUP] 35 [/SUP], Peter B Gilbert[SUP] 1 2 3 [/SUP], Dean Follmann[SUP] 36 [/SUP]; Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team
Affiliations
Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. Consistently across the Moderna and Pfizer-BioNTech vaccine platforms and across all variant Spike inserts assessed, both peak and exposure-proximal ("predicted-at-exposure") titers correlated with lower Omicron COVID-19 risk in individuals previously infected with SARS-CoV-2, albeit significantly less so in naïve individuals [e.g., exposure-proximal hazard ratio per 10-fold increase in BA.1 titer 0.74 (95% CI 0.59, 0.94) for naïve vs. 0.41 (95% CI 0.23, 0.64) for non-naïve; interaction p = 0.013]. Neutralizing antibody titer was a strong inverse correlate of Omicron COVID-19 in non-naïve individuals and a weaker correlate in naïve individuals, posing questions about how prior infection alters the neutralization correlate.
. 2025 Jan 17;16(1):759.
doi: 10.1038/s41467-025-55931-w. Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost
Bo Zhang[SUP] 1 [/SUP], Youyi Fong[SUP] 1 2 3 [/SUP], Lauren Dang[SUP] 4 [/SUP], Jonathan Fintzi[SUP] 4 [/SUP], Shiyu Chen[SUP] 1 [/SUP], Jing Wang[SUP] 5 [/SUP], Nadine G Rouphael[SUP] 6 [/SUP], Angela R Branche[SUP] 7 [/SUP], David J Diemert[SUP] 8 [/SUP], Ann R Falsey[SUP] 7 [/SUP], Daniel S Graciaa[SUP] 6 [/SUP], Lindsey R Baden[SUP] 9 [/SUP], Sharon E Frey[SUP] 10 [/SUP], Jennifer A Whitaker[SUP] 11 [/SUP], Susan J Little[SUP] 12 [/SUP], Satoshi Kamidani[SUP] 13 14 [/SUP], Emmanuel B Walter[SUP] 15 [/SUP], Richard M Novak[SUP] 16 [/SUP], Richard Rupp[SUP] 17 [/SUP], Lisa A Jackson[SUP] 18 [/SUP], Chenchen Yu[SUP] 1 [/SUP], Craig A Magaret[SUP] 1 [/SUP], Cindy Molitor[SUP] 1 [/SUP], Bhavesh Borate[SUP] 1 [/SUP], Sydney Busch[SUP] 19 [/SUP], David Benkeser[SUP] 19 [/SUP], Antonia Netzl[SUP] 20 [/SUP], Derek J Smith[SUP] 20 [/SUP], Tara M Babu[SUP] 21 [/SUP], Angelica C Kottkamp[SUP] 22 [/SUP], Anne F Luetkemeyer[SUP] 23 [/SUP], Lilly C Immergluck[SUP] 24 25 [/SUP], Rachel M Presti[SUP] 26 [/SUP], Martín Bäcker[SUP] 27 [/SUP], Patricia L Winokur[SUP] 28 [/SUP], Siham M Mahgoub[SUP] 29 [/SUP], Paul A Goepfert[SUP] 30 [/SUP], Dahlene N Fusco[SUP] 31 [/SUP], Robert L Atmar[SUP] 11 [/SUP], Christine M Posavad[SUP] 32 33 [/SUP], Jinjian Mu[SUP] 34 [/SUP], Mat Makowski[SUP] 34 [/SUP], Mamodikoe K Makhene[SUP] 35 [/SUP], Seema U Nayak[SUP] 35 [/SUP], Paul C Roberts[SUP] 35 [/SUP], Peter B Gilbert[SUP] 1 2 3 [/SUP], Dean Follmann[SUP] 36 [/SUP]; Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team
Affiliations
- PMID: 39824819
- DOI: 10.1038/s41467-025-55931-w
Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. Consistently across the Moderna and Pfizer-BioNTech vaccine platforms and across all variant Spike inserts assessed, both peak and exposure-proximal ("predicted-at-exposure") titers correlated with lower Omicron COVID-19 risk in individuals previously infected with SARS-CoV-2, albeit significantly less so in naïve individuals [e.g., exposure-proximal hazard ratio per 10-fold increase in BA.1 titer 0.74 (95% CI 0.59, 0.94) for naïve vs. 0.41 (95% CI 0.23, 0.64) for non-naïve; interaction p = 0.013]. Neutralizing antibody titer was a strong inverse correlate of Omicron COVID-19 in non-naïve individuals and a weaker correlate in naïve individuals, posing questions about how prior infection alters the neutralization correlate.