Evidence map›Paper›PMID 41698311›Full record

Trial reportVaccine2026

The neutralizing antibody titer correlate of COVID-19 risk in the COVID-19 variant immunologic landscape (COVAIL) trial was not modified by SARS-CoV-2 amino acid sequence distances.

Fei Heng, Craig A Magaret, Nadine G Rouphael, Angela R Branche, Youyi Fong, Lindsay N Carpp, Chenchen Yu, Shiyu Chen, Bo Zhang, David J Diemert and 32 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Vaccine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05289037 (Phase 2 Clinical Trial to Optimize Immune Coverage of SARS-CoV-2 Existing and Emerging Variants), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05289037 phase2completednot on this map

Phase 2 Clinical Trial to Optimize Immune Coverage of SARS-CoV-2 Existing and Emerging Variants

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2022 to 2023Enrolled1,270ConditionsCOVID-19ArmsAS03, BNT162b2, BNT162b2 (B.1.1.529), BNT162b2 (B.1.351), BNT162b2 bivalent (wildtype and Omicron BA.1)
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

42 authors.

Fei HengDepartment of Mathematics and Statistics, University of North Florida, Jacksonville, FL, USA.
Craig A MagaretVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Nadine G RouphaelHope Clinic, Emory University, Decatur, GA, USA.
Angela R BrancheVaccine and Treatment Evaluation Unit, University of Rochester, Rochester, NY, USA.
Youyi FongVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
Lindsay N CarppVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Chenchen YuVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Shiyu ChenVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Bo ZhangVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
David J DiemertGeorge Washington Vaccine Research Unit, George Washington University, Washington, DC, USA.
Ann R FalseyVaccine and Treatment Evaluation Unit, University of Rochester, Rochester, NY, USA.
Daniel S GraciaaHope Clinic, Emory University, Decatur, GA, USA.
Lindsey R BadenDepartment of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Sharon E FreyCenter for Vaccine Development, Saint Louis University, MO, USA.
Jennifer A WhitakerDepartment of Molecular Virology and Microbiology and Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Susan J LittleDivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California, La Jolla, San Diego, CA, USA.
Satoshi KamidaniCenter for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, GA, USA; Department of Pediatrics, Emory University, Atlanta, GA, USA.
Emmanuel B WalterDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
Richard M NovakProject WISH, University of Illinois at Chicago, Chicago, IL, USA.
Richard RuppDepartment of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
Lisa A JacksonKaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
Tara M BabuDivision of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA.
Angelica C KottkampVaccine and Treatment Evaluation Unit, Manhattan Research Clinic, New York University Grossman School of Medicine, New York, NY, USA.
Anne F LuetkemeyerDivision of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco, CA, USA.
Lilly C ImmergluckClinical Research Center, Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA, USA.
Rachel M PrestiDepartment of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Martín BäckerVaccine and Treatment Evaluation Unit, Long Island Research Clinic, New York University, Long Island School of Medicine, Mineola, NY, USA.
Patricia L WinokurDepartment of Medicine, University of Iowa College of Medicine, Iowa City, IA, USA.
Siham M MahgoubHoward University College of Medicine, Howard University Hospital, Washington, DC, USA.
Paul A GoepfertDepartment of Medicine, University of Alabama at Birmingham, AL, USA.
Dahlene N FuscoDepartment of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Robert L AtmarDepartment of Molecular Virology and Microbiology and Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Christine M PosavadInfectious Diseases Clinical Research Consortium (IDCRC) Laboratory Operations Unit, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Jinjian MuThe Emmes Company, LLC, Rockville, MD, USA.
Mat MakowskiThe Emmes Company, LLC, Rockville, MD, USA.
Mamodikoe K MakheneDivision of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Seema U NayakDivision of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Viviana SimonDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Harm van BakelDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Artificial Intelligence and Human Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Paul C RobertsDivision of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Peter B GilbertVaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA. Electronic address: pgilbert@fredhutch.org.
Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team

Funding

Statistical Methods in HIV Vaccine Efficacy TrialsR37AI054165 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Peter B. Gilbert · 2010 to 2026
$6.7M
NIAID NIH HHS R37 AI054165
6 · The paper itself

Abstract

In the Coronavirus Variant Immunologic Landscape Trial (COVAIL) conducted in the United States in 2022-2023, 985 participants received a second COVID-19 booster with one of twelve monovalent or bivalent mRNA inserts. Pseudovirus serum inhibitory dilution 50% neutralizing antibody titer (nAb titer) measured two-weeks post booster significantly associated with lower COVID-19 incidence over six months follow-up in this trial. COVAIL investigators sequenced SARS-CoV-2 Spike amino acid sequences for all COVID-19 cases, with a sequence successfully obtained from 129 of 195 cases. For COVID-19 endpoint cases we calculated five distances of the case-causing sequence to a reference sequence, the first two physico-chemical weighted Hamming distances of Spike or receptor binding domain (RBD) to a participant's nearest Spike or RBD vaccine-insert sequence, and the other three estimated degrees of neutralizing antibody escape from the XBB.1.5 RBD strain calculated with deep mutational scanning. Hypothesizing that the nAb titer correlate of risk may have a stronger association with COVID-19 when focusing on COVID-19 infections more closely matched to the vaccine insert in Spike or RBD amino acid sequence or with lower RBD antibody escape score, we tested this hypothesis for the combined group receiving a monovalent Prototype (ancestral strain) booster (n = 143) and for the combined group receiving an Omicron-containing booster (n = 744). For both combined groups, the nAb titer correlate of risk did not significantly vary across any of the assessed sequence distances from the vaccine insert (all p-values >0.10), although RBD Hamming distance had point estimates consistent with a weakening correlate with distance, motivating further exploration in settings with greater antigenic heterogeneity. Indeed, statistical power was bounded by the limited antigenic variability of viruses infecting trial participants over the follow-up period (April 21, 2022 to May 25, 2023), which spanned only a 3.02-fold nAb titer range of differential sensitivity to sera from XBB.1.5-infected individuals. ClinicalTrials.gov Identifier: NCT05289037.

Indexed as

Antibodies, NeutralizingAntibodies, ViralCOVID-19COVID-19 VaccinesSARS-CoV-2Amino Acid SequenceHumansImmunization, SecondarySpike Glycoprotein, CoronavirusAntibodies, NeutralizingAntibodies, ViralCOVID-19 VaccinesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Deep mutational scanningImmune correlate of protectionmRNA vaccineNeutralizing antibody escapeRandomized clinical trialRecombinant protein vaccine

Identifiers

PMID41698311
PMCPMC13008134

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.