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Peer reviewedOpen accessSARSCOVID-19Gastroenteritis

A phase I, needle free, dose escalation clinical trial of pEVAC-PS, a candidate pan-Sarbecovirus Vaccine

Journal of Infection·

Alasdair PS Munro, Matteo Ferrari, Rebecca Kinsley, Daniel Egan, Sneha Vishwanath, Thomas Bower, Andrew Chan, Matthew Davies, Joanne Marie M. Del Rosario, Ron Moss, Yvanne Enever, Benedict Asbach, Ralf Wagner, Rachel Bousfield, Krishna Chatterjee, Victoria Cornelius, Saul N. Faust, Jonathan L. Heeney

DOI
10.1016/j.jinf.2026.106759
PMID
42155675
PMCID
OpenAlex
W4409983444
Study type
Journal article
Publisher
Elsevier BV
Article type
journal-article
Integrity
current

Why this research matters now

This candidate demonstrates feasibility of a computationally designed pan-Sarbecovirus vaccine approach that could potentially address multiple coronaviruses, including future zoonotic spillovers. The thermostable, needle-free delivery platform may support deployment in resource-limited settings.

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Structured evidence summary

Research question

This Phase I trial evaluated the safety, tolerability, and immunogenicity of pEVAC-PS, a computationally designed pan-Sarbecovirus vaccine candidate intended to induce broad cross-protection against SARS, SARS-CoV-2, and related coronaviruses with zoonotic potential.

Study design

An open-label Phase I dose escalation trial administered the DNA vaccine via needle-free intradermal delivery at four dose levels (0.2 to 1.2 mg) on days 0 and 28. Primary outcomes assessed safety and reactogenicity; secondary outcomes measured humoral immunogenicity at day 56.

Population and setting

Thirty-nine healthy volunteers aged 18 to 50, previously vaccinated with two or three COVID-19 doses and without recent confirmed infection, were enrolled sequentially across cohorts between December 2021 and September 2023.

Main findings

The vaccine was well tolerated at all dose levels with no significant safety concerns. Participants developed measurable responses to conserved sarbecovirus epitopes encoded by the vaccine. However, interpretation of immunogenicity was complicated by high baseline antibody levels and ongoing Omicron variant transmission during recruitment.

Public-health relevance

This candidate demonstrates feasibility of a computationally designed pan-Sarbecovirus vaccine approach that could potentially address multiple coronaviruses, including future zoonotic spillovers. The thermostable, needle-free delivery platform may support deployment in resource-limited settings.

Important limitations

The immunogenicity findings are limited by high pre-existing immunity from prior vaccination and infection, heterogeneous exposure histories across cohorts, and ongoing Omicron variant circulation during enrollment, which introduced unavoidable immune bias affecting interpretation of vaccine-induced responses.

GIDS interpretation

This first-in-human data supports proceeding to further evaluation of this antigen design strategy; however, these early-phase findings cannot be generalized beyond the studied population or interpreted as confirmatory of protective efficacy against specific sarbecovirus threats. The study was not designed to evaluate effectiveness against any particular surveillance signal or outbreak context.

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Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

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Evidence relationships

This article has 13 auditable classifier relationships to diseases, places, topics, and study design.

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