World's First Coxsackievirus Vaccine Just Passed a Big Test
Review written by: Roshni Kadam
Coxsackievirus B (CVB) represents a substantial public health burden, causing illness across all age groups from infants to adults. Symptoms range from mild respiratory disease to severe, life-threatening illness such as meningitis, encephalitis, myocarditis, and hand-foot-mouth disease. CVB has also been linked to chronic diseases cardiomyopathy, type 1 diabetes, and celiac disease, where persistent infection is thought to sustain in the heart, pancreas, and gut mucosa, respectively. Despite this disease burden, no CVB-specific vaccine currently exists as a preventive measure. PRV-101, a pentavalent (CVB1–5) formalin-inactivated whole-virus vaccine with no adjuvant, was developed and tested by Provention Bio, Inc and was later acquired by Sanofi Bridgewater NJ, in the first-in-human phase 1 trial, PROVENT. Three immunizations given 1 month apart induced a dose-dependent antibody response and were not associated with vaccine-related severe adverse effects, demonstrating good immunogenicity and tolerability.
To assess whether this protection was durable, 26 of the original 32 PROVENT participants (11 high-dose, 10 low-dose, 5 placebo) returned for a follow-up visit approximately 2 years post-vaccination (PROVENT-IIS), where blood was collected and serum isolated for CVB antibody and autoantibody testing. Virus type specific neutralizing antibodies against the CVB strains in PRV-101 were measured by plaque reduction neutralizing antibody assay, and IgG/IgM class CVB antibody levels were measured by ELISA (Serion ELISA, based on recombinant VP1 antigens from CVB1, CVB3, and CVB5. A crucial point to consider is that this assay detects antibodies that cross-react across CVB serotypes rather than distinguishing individual types).
Protection remained clearly dose-dependent: participants who received the higher vaccine dose maintained higher neutralizing antibody titers at 2 years than the low-dose group, with most reaching levels considered protective against enterovirus infection. This antibody durability levels persisting 2 years after the last dose suggests PRV-101 efficiently induces memory B cells. Encouragingly, importantly, all follow-up participants remained negative for type 1 diabetes and celiac disease associated autoantibodies, and none developed new chronic disease, despite nearly half the cohort carrying HLA-conferred genetic risk for these conditions. However, a few caveats remain that future studies will need to address. First, because neutralizing antibodies are considered a marker of past CVB exposure, some of the durable response in "baseline seronegative" participants may reflect boosting of pre-existing CVB-specific memory T cells from earlier natural infection, rather than purely vaccine-induced priming. Second, the cohort size is small, larger trials are needed to confirm these findings. However, no vaccine has ever existed for coxsackievirus B until now. This isn't the finish line, but it's a big step toward one.
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Laiho JE, Lehtonen JP, Puustinen L, Kääriäinen S, Härkönen T, Oikarinen S, León F, Sanjuan M, Scheinin M, Knip M, Hyöty H. Safety and Immunogenicity of a Vaccine Against Coxsackieviruses B (PRV-101)-Follow-up of the First-in-Human Phase 1 Trial. Open Forum Infect Dis. 2026 May 13;13(5):ofag277. doi: 10.1093/ofid/ofag277. PMID: 42205598; PMCID: PMC13209955.
