Mpox Immunity May Wane Over Time, Raising Questions for Long-Term Infection Prevention Planning

New research examining long-term immune responses following mpox infection or vaccination suggests that protective antibody levels decline substantially over time, a finding with important implications for infection prevention and control (IPC) programs. The study evaluated the persistence of mpox virus-specific neutralizing antibodies more than 2 years after either natural infection or vaccination with Modified Vaccinia Ankara Bavarian Nordic (MVA-BN).

The study, published in The Journal of Infectious Diseases, is titled “A Humoral Dilemma: Reassessing Monkeypox Virus Neutralizing Antibodies at More Than Two Years From Mpox or MVA-BN Vaccination,” and was led by researchers at Vita-Salute San Raffaele University in Milan, Italy.

For IPC professionals responsible for outbreak preparedness, occupational health policies, and vaccination strategies, the findings highlight the challenges of relying on long-term immunity for protection against Mpox in health care settings.

The retrospective analysis included 90 men who had previously experienced Mpox infection or had received MVA-BN vaccination (48 with prior mpox infection and 42 who received Jynneos vaccination). All participants had antibody levels measured 6 months after infection or vaccination and were followed up again more than 2 years later. Neutralizing antibody titers were assessed by plaque-reduction neutralization testing, with positivity defined by specific dilution thresholds.

At more than 2 years, antibody levels remained limited. Many participants, whether previously infected or vaccinated, showed low or undetectable antibody levels—though those with prior infection were more likely to still have some detectable antibodies (33 out of 48 [68.8%] vs 20 out of 42 [47.6%]). These findings suggest that immune protection diminishes over time in many people, whether immunity was obtained through infection or vaccination.

At the lower threshold, individuals with prior mpox infection were more likely to have detectable antibodies than those who had only been vaccinated. However, the difference was modest. The strongest predictor of long-term antibody detection was not recent infection but historical smallpox vaccination. Participants who had previously received smallpox vaccine decades earlier were significantly more likely to retain detectable neutralizing antibodies for more than 2 years.

Antibody levels at 6 months were also important. Individuals with higher neutralizing antibody titers early after infection or vaccination were more likely to have detectable antibodies later. This finding suggests that the strength of the early immune response may influence durability, although antibody levels still declined for many participants over time.

From an infection prevention standpoint, the results reinforce that neither prior mpox infection nor vaccination should be assumed to provide long-lasting protection. This is particularly relevant for health care workers in high-risk settings, including emergency departments, infectious disease units, and laboratories that may encounter orthopoxviruses.

The authors conclude that “MPXV-specific NAbs waned at more than 2 years from previous infection or vaccination, often becoming undetectable.” For IPC teams, this underscores the importance of continued vigilance even among previously infected or vaccinated staff. Reliance on presumed immunity alone may leave gaps in protection during future outbreaks.

These findings also have implications for booster policies, exposure risk assessments, and postexposure management protocols. IPC professionals may need to work closely with occupational health and public health partners to determine when additional vaccination or enhanced precautions are warranted, particularly as the time since vaccination increases.

While antibody levels are only a single component of immune protection, the decline observed in this study underscores the need for layered prevention strategies. Standard and transmission-based precautions, early case identification, proper use of personal protective equipment, and staff education remain essential tools for preventing mpox transmission in health care settings.

As mpox continues to pose an intermittent threat, understanding the limits of long-term immunity will be critical for informed IPC decision-making and sustained preparedness.