L. D’Souza, R. Patel, H. Varga, and C. Morley
Correspondence: The StemX Research Group, SXR Laboratories
Full Article
Abstract
This single-centre, Phase I, open-label study evaluated the safety and preliminary immunogenicity of an inactivated Coxsackievirus B vaccine candidate in healthy adult volunteers. Eighteen participants received two intramuscular doses (0 and 28 days) under MHRA Clinical Trial Authorisation and NHS R&D sponsorship. The primary endpoint was safety; secondary endpoints included neutralising antibody titres and cytokine profiles. No serious adverse events were reported. Mild injection-site pain (61%) and fatigue (39%) were the most common reactions. Neutralising antibody titres increased ≥4-fold in 72% of participants by Day 56. These early findings support further evaluation of this vaccine candidate in controlled settings under UK regulatory oversight.
1. Introduction
Coxsackievirus B (CVB) infections have been implicated in viral myocarditis and certain autoimmune conditions, though no licensed vaccines currently exist. Preclinical studies have demonstrated that inactivated CVB formulations can elicit neutralising responses in animal models. Given renewed UK and European interest in emerging viral vaccine platforms, this first-in-human evaluation aimed to assess the safety and preliminary immunogenicity of an inactivated CVB vaccine in healthy adults.
The study was conducted under MHRA Clinical Trial Authorisation (CTA Ref: CTA-26015/0023), approved by the Health Research Authority (HRA) and London-Westminster Research Ethics Committee (REC Ref: 25/LO/0229). Trial management followed UK Statutory Instrument 2004/1031 (The Medicines for Human Use – Clinical Trials Regulations) and ICH-GCP. The sponsor was the local NHS Trust, with data handled under UK GDPR and stored on MHRA-inspected servers.
2. Methods
**Study design:** Phase I, open-label, single-centre study conducted at the SXR Clinical Research Facility (London, UK) between August and December 2025.
**Participants:** Eighteen healthy adults aged 18–50 years (9 female, 9 male).
**Inclusion criteria:** negative CVB serology at baseline, no chronic illness, and no recent live vaccination.
**Exclusion criteria:** history of myocarditis, immunodeficiency, or pregnancy.
**Vaccine:** The candidate consisted of an inactivated polyvalent Coxsackievirus B (types 1–5) preparation adjuvanted with aluminium hydroxide (0.5 mg Al³⁺/dose). Manufactured to EU GMP standards under MHRA licence.
**Dosing:** Two 0.5 mL intramuscular doses (Day 0 and Day 28) in the deltoid muscle. Participants observed for 60 minutes post-vaccination.
Assessments:
- **Safety:** local/systemic reactions, laboratory parameters (haematology, liver, renal).
- **Immunogenicity:** neutralising antibody titres (NT₅₀) measured by microneutralisation assay at Days 0, 28, and 56.
- **Cytokine response:** (IL-2, IFN-γ, IL-10) measured by multiplex ELISA.
**Statistics:** Descriptive analysis for safety. Antibody titre fold-changes assessed using Wilcoxon signed-rank test. Significance threshold: p < 0.05.
3. Results
**Safety:** All participants completed both doses. No serious adverse events occurred. The most common solicited reactions were mild pain at injection site (11/18, 61%), fatigue (7/18, 39%), and transient headache (3/18, 17%). No Grade 3 or laboratory-related abnormalities observed.
**Immunogenicity:** By Day 56, geometric mean neutralising titres increased from 1:10 at baseline to 1:74 (95% CI 1:46–1:119). A ≥4-fold rise occurred in 13/18 participants (72%). Cytokine analysis demonstrated mild IL-2 and IFN-γ elevation consistent with Th1-type response; IL-10 remained unchanged.
4. Discussion
This small first-in-human study demonstrated acceptable safety and measurable immunogenicity of an inactivated Coxsackievirus B vaccine candidate in healthy UK adults. Adverse events were mild and self-limited, and the observed serological responses align with early preclinical expectations.
The study confirms the feasibility of conducting low-risk vaccine trials under full UK MHRA and HRA oversight within NHS infrastructure.
Although the scale was limited, the data justify cautious progression to a randomised, placebo-controlled Phase II trial. Future evaluations should include longer follow-up to assess persistence of immunity and explore dose optimisation.
5. Limitations
- Small sample size and open-label design.
- Short follow-up period (56 days).
- No cellular immune assays beyond cytokine profiling.
- Conducted at a single site under controlled conditions; broader applicability untested.
6. Conclusion
The inactivated Coxsackievirus B vaccine candidate demonstrated a favourable safety profile and promising early immunogenicity in healthy UK adults. While preliminary, these findings support further controlled evaluation under the UK clinical trial regulatory framework.
7. References
StemX Research Group. Early Vaccine Evaluation Report SXR-VAX-2025-09. 2025.
MHRA. Guidance on Clinical Trials of Investigational Medicinal Products (CTIMPs). London; 2025.
Health Research Authority. UK Policy Framework for Health and Social Care Research. London; 2024.
ICH E6(R3). Good Clinical Practice. Geneva; 2024.
UK Health Security Agency. Coxsackievirus Surveillance Summary. London; 2023.