When a child receives two doses of the measles, mumps, and rubella (MMR) vaccine, the prevailing assumption is that they are protected. But vaccination coverage and actual immunity are not the same thing — and a new study from India makes that distinction with troubling clarity. Published in JAMA Network Open, the research from investigators at Mayo Clinic, the BRIC-Rajiv Gandhi Centre for Biotechnology in Kerala, and Emory University School of Medicine found that a meaningful proportion of fully vaccinated Indian children lack sufficient antibody levels to be considered protected against measles, raising urgent questions about how elimination goals are being measured and pursued.
The study enrolled 684 children who had each received at least two doses of a measles-containing vaccine, along with 544 of their mothers, drawn from the southern Indian states of Kerala and Tamil Nadu. Researchers measured measles-specific IgG antibodies, IgM antibodies, and — critically — neutralizing antibody titers, which are the most direct immunological correlate of protection against measles infection. A neutralizing antibody titer of 120 mIU/mL or above was used as the threshold for protective immunity.
One in Eleven Vaccinated Children Lack Protective Immunity
The findings challenge a central assumption underlying India’s measles elimination strategy: that achieving high two-dose vaccination coverage translates to population-level protection. Despite every child in the cohort having received at least two doses — and nearly two-thirds having received a third — only 90.8% tested positive for measles-specific IgG antibodies, and only 91.5% had neutralizing antibody titers at or above the protective threshold. Both figures fall below the 95% coverage benchmark generally considered necessary for herd immunity. Put differently, roughly one in eleven vaccinated children in this sample lacked demonstrable immunological protection against one of the most contagious pathogens known to medicine.
The picture becomes more complex when IgM data are considered. Measles-specific IgM — an indicator of recent or active infection — was detected in 13% of vaccinated children, with another 13.2% yielding borderline results. In the absence of vaccination records confirming a recent booster, researchers interpreted IgM positivity as likely evidence of recent exposure to circulating measles virus, a finding consistent with India’s continued status as one of the world’s leading contributors to global measles burden. Mothers in the cohort, by contrast, showed considerably stronger immunity, with 94.8% achieving protective neutralizing antibody titers — levels that likely reflect a combination of prior natural infection and immune maturation over time.
Male Children Show Lower Immune Response to Vaccination
The study also identified a notable sex-based disparity in vaccine-induced immunity. Female children had significantly higher neutralizing antibody and IgG titers than their male counterparts, a finding consistent with prior literature and a 2022 meta-analysis reporting higher measles incidence in boys across multiple countries. Among the 58 children whose neutralizing antibody titers fell below the protective threshold, male children were disproportionately represented. Notably, none of the seven children who had received four vaccine doses fell below the protective threshold — a pattern the authors suggest may warrant consideration of targeted booster strategies, particularly for male children.
The researchers conducted a cross-sectional observational study, recruiting participants from nursery schools, secondary schools, residential associations, and hospital outpatient settings during non-infectious illness visits. Antibody titers were measured using validated commercial ELISA kits alongside a fluorescence-based plaque reduction microneutralization assay calibrated against international standards. The study followed STROBE reporting guidelines for cross-sectional studies.
Several limitations are worth noting. Vaccination records were largely unavailable for the maternal cohort, limiting analysis of dose-response relationships in that group. Additionally, the absence of clinical records documenting prior measles infection made it impossible to fully distinguish vaccine-induced from infection-induced immunity, or to confirm the source of IgM positivity in affected children.
Findings Expose Critical Gaps in Global Outbreak Preparedness
The public health and biosecurity implications of these findings extend well beyond India. With a basic reproduction number of approximately 18 in susceptible populations, a single measles case can infect nearly two dozen unprotected individuals in close contact. India remains a major source of measles importations that seed outbreaks globally, including in the United States. If national vaccination coverage statistics are being used as a proxy for herd immunity without accounting for suboptimal immune responses, then both India and the international community may be operating with a dangerously incomplete picture of actual population vulnerability. For biosecurity planners and global health security practitioners, this study is a pointed reminder that immunization program metrics must evolve beyond coverage rates to incorporate serological surveillance. Knowing how many children were vaccinated is not the same as knowing how many are protected.
Sources and further reading:
Quach HQ, Jones SP, Joseph I, et al. Low Measles Seropositivity in Vaccinated Children. JAMA Network Open. August 27, 2025