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. 2025 Aug 1;8(8):e2529409.
doi: 10.1001/jamanetworkopen.2025.29409.

Low Measles Seropositivity in Vaccinated Children

Huy Quang Quach  1 , Sara P Jones  2 , Iype Joseph  2 , Alexandria J Powell  1 , Inna G Ovsyannikova  1 , Nathaniel D Warner  3 , Diane E Grill  3 , John B Johnson  2 , Remya Vasanthi Sasi  2 , Archana Mohankumar Ajithakumari  2 , Raji Prasad  2 , Remya Reveendran  2 , Jayalekshmi Devakikutty  2 , Vishnu Vikraman Mohanakumari  2 , Gregory A Poland  1 , M Radhakrishna Pillai  2 , Joshy Jacob  4 , Richard B Kennedy  1
Affiliations

Low Measles Seropositivity in Vaccinated Children

Huy Quang Quach et al. JAMA Netw Open. .

Abstract

Importance: India's goal of measles elimination remains unmet, as evidenced by significant recent outbreaks.

Objective: To identify seroprevalence rates among vaccinated children and to examine demographic factors that influence antibody responses.

Design, setting, and participants: This cross-sectional study included a highly vaccinated cohort of Indian children from the states of Kerala and Tamil Nadu between 2018 and 2023. Eligible children had received at least 2 doses of measles-containing vaccines; their mothers were recruited from various community settings, including local nursery and secondary schools, residential associations, and hospitals.

Exposure: Measles-specific antibodies were quantified in serum samples.

Main outcomes and measures: Measles-specific immunoglobulin G (IgG) and neutralizing antibodies were quantified in both children and mothers. Measles-specific IgM was also measured in children.

Results: The total cohort comprised 684 children (median age, 9 years [range, 4-18 years]; 348 male [50.1%]) and 544 mothers. All children received at least 2 doses of measles-containing vaccines; 435 children (63.6%) received a third dose, and 7 (1.0%) received a fourth dose. Among the children, 621 (90.8%) had positive measles-specific IgG, and 623 (91.5%) had protective neutralizing antibodies titers, with a strong correlation between measles-specific IgG and neutralizing antibodies (r = 0.73; P < .001). Female children exhibited significantly higher titers of both measles-specific IgG and neutralizing antibodies compared with male children. While IgG and neutralizing antibody titers remained stable over time and were not associated with the number of vaccine doses in children, neutralizing antibody titers increased with age in mothers, likely due to repeated viral exposure. Notably, in 20 families with at least 2 children, differential measles-specific IgM profiles were observed between siblings despite high IgG and neutralizing antibody titers, suggesting ongoing breakthrough infections.

Conclusions and relevance: In this cross-sectional study, substantial measles immunity gaps were found despite high vaccine coverage with evidence of breakthrough infections, posing significant challenges to India's measles elimination efforts. These results underscore the urgent need to strengthen India's immunization program and investigate the mechanisms driving suboptimal responses to measles vaccination; without addressing these immune response deficiencies, achieving measles elimination through increased vaccine coverage alone may remain unattainable in India.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Pillai reported grants from Rajiv Gandhi Centre for Biotechnology during the conduct of the study. Dr Poland serves as chair of a safety evaluation committee for novel investigational vaccine trials being conducted by Merck Research Laboratories; he reported consulting work with AiZtech, Emergent Biosolutions, GlaxoSmithKline, Invivyd, Janssen Global Services LLC, Merck & Co Inc, Moderna, Novavax, and Syneos Health and he reported holding patents related to vaccinia, influenza, and measles peptide vaccines outside the submitted work. Drs Poland, Kennedy, and Ovsyannikova reported receiving grant funding and royalties from ICW Ventures and to having a pending patent related to COVID-19 peptide-based vaccines outside the submitted work; Drs Poland, Kennedy, and Ovsyannikova also hold a patent issued with Mayo Clinic on genetic variations influencing immune responses to measles vaccination. Dr Kennedy reported advisory work on vaccine development with Merck & Co and Sanofi Pasteur outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association of Sex With Measles-Specific Antibodies in the Child Cohort
A and C, The horizontal red dashed line and the vertical red dashed line represent the positivity threshold for measles-specific neutralizing antibodies (120 mIU/mL). B and C, The horizontal red line indicates the positivity threshold for measles-specific IgG (11 units/mL). D, The vertical red dashed line represents the positivity threshold for measles-specific immunoglobulin M (IgM) (11 units/mL).
Figure 2.
Figure 2.. Time Since Vaccination and Number of Vaccine Dose on Measles-Specific Antibodies in the Child Cohort
C, The horizontal red dashed line represents the positivity threshold for measle-specific neutralizing antibodies (120 mIU/mL). D, The horizontal red line represents the positivity threshold for measles-specific immunoglobulin G (IgG) (11 units/mL).
Figure 3.
Figure 3.. Correlations Between Measles-Specific Antibodies in Mothers and Their Children
Figure 4.
Figure 4.. Differential Measles-Specific Immunoglobulin M (IgM) Profiles in Families With 2 or More Children
In each of 20 families analyzed, 1 child tested negative while other siblings tested positive for measles-specific IgM. Despite this difference, IgM-negative and IgM-positive children had comparable titers of measles-specific nAb and measles-specific IgG. A and B, The red dashed lines in represent the positivity threshold for measles-specific neutralizing antibodies (120 mIU/mL) and measles-specific IgG (11 units/mL), respectively. The gray lines connect data points for children and mothers within the same household.
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