What is the best course of action for a patient who experienced fever and injection site swelling after the first dose of the smallpox and Mpox live, non-replicating vaccine, regarding their second vaccine dose?

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Mpox Vaccination: Second Dose Recommendation After Mild Adverse Reactions

This patient should receive his second vaccine dose as soon as possible (Answer C). The fever and injection site swelling he experienced are expected, normal reactions to the first dose of JYNNEOS vaccine and do not contraindicate completion of the two-dose series.

Why These Reactions Are Not Concerning

  • Fever and injection site reactions are common expected responses to JYNNEOS vaccination, occurring in the majority of recipients and representing normal immune activation rather than contraindications to further vaccination 1.

  • Fever occurs in approximately 70% of primary vaccinees, with temperatures >100°F for 4-14 days after vaccination being a typical response 1.

  • Injection site swelling and tenderness are expected normal reactions that begin 3-10 days after vaccination and can persist for 2-4 weeks, resolving spontaneously without intervention 1, 2.

  • These mild local and systemic reactions do not predict severe adverse events and should not delay or prevent completion of the vaccine series 3.

Why Two Doses Are Essential

  • A two-dose series of JYNNEOS is the standard recommendation for persons aged ≥18 years at risk for mpox, with doses administered 28 days apart 4, 3.

  • Single-dose protection is insufficient - the complete two-dose series is required to achieve optimal immunity against mpox infection 4.

  • Post-exposure prophylaxis studies demonstrate high vaccine effectiveness (88.8% overall, 93.6% for non-cohabitant sexual contacts) when the series is completed, supporting the importance of receiving both doses 5.

Timing Considerations

  • The patient is already three months past his first dose, which is well beyond the recommended 28-day interval but still appropriate for completing the series 4, 3.

  • There is no need to restart the vaccine series - delayed second doses are still valid and effective, and the series should simply be completed rather than restarted 4.

Safety Profile Supports Continuation

  • Postlicensure surveillance of 987,294 JYNNEOS doses found that the most common adverse events were nonserious injection site reactions consistent with prelicensure studies 3.

  • Serious adverse events were rare in adults, and the safety profile supports completion of the two-dose series even in those who experienced mild reactions after dose one 3.

  • No evidence suggests increased risk of severe reactions with the second dose in patients who had mild local or systemic reactions to the first dose 3.

What to Avoid

  • Do not delay the second dose further - this patient is already overdue and should complete the series promptly to achieve full protection 4.

  • Do not switch to a live, replicating vaccine (Answer D is incorrect) - JYNNEOS is a live, non-replicating vaccine, and switching vaccine types mid-series is not recommended and could compromise immunity 4.

  • Do not consider him adequately protected with one dose (Answer A is incorrect) - single-dose protection is suboptimal and the two-dose series is required 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Management of Adverse Reactions After Monkey Bite Vaccination

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Post-exposure vaccine effectiveness and contact management in the mpox outbreak, Madrid, Spain, May to August 2022.

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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