Measles immunity gaps: distinct serological profiles from the United States and India

Abstract

Sustained measles elimination requires high herd immunity, maintained through vaccination and verified by global serosurveillance. Comparing measles neutralizing antibody titres in US and Indian populations, we identified distinct age-specific and country-specific trends. These findings highlight the urgent need for tailored strategies to strengthen population immunity and global measles control efforts.

Achieving measles elimination requires >95% herd immunity due to the virus’s high transmissibility,¹ as well as global coordination to prevent travel-related outbreaks.² In this communication, we highlight the challenges of sustained elimination by comparing measles-specific neutralizing antibody (nAb) titres in the USA and India—two countries with contrasting epidemiological profiles. The USA has maintained measles elimination status since 2000 but faces ongoing threats from declining vaccination rates and imported cases, while India has yet to achieve elimination with regular outbreaks contributing to the global measles burden.

We analysed measles-specific nAb titres in 2490 individuals across two children and two adult cohorts from the USA and India using a plaque reduction microneutralization assay (Supplementary Material). US children had significantly higher median nAb titre (888.5 mIU/ml) than Indian children (422.4 mIU/ml; P < 0.001, Figure 1A), with only 2.4% falling below the protective threshold of 120 mIU/ml,³ compared to 8.52% in India. In contrast, US adults had significantly lower nAb titres (534.9 mIU/ml) than Indian adults (1421.1 mIU/ml; P < 0.001, Figure 1B). It is important to note that Indian adult cohort consisted exclusively of female participants (Supplementary Table S1), whereas US adult cohort included both males and females. To account for this difference, we conducted a separate analysis of US female participants, which confirmed the same trend (P < 0.001, Figure 1C).

Figure 1.

Seroprevalence of measles-specific nAbs. (A) US children (n = 1024) had higher nAb titres compared to Indian children (n = 684). (B) In contrast, US adults (n = 238) had lower nAb titres than Indian adults (n = 544). (C) Since the Indian adult cohort consisted of only females, nAb titres between US female adults (n = 151) and Indian female adults (n = 544) were compared separately. Dashed lines in Figures A, B, and C represent the protective nAb titre threshold of 120 mIU/ml. (D) Correlation between nAb levels and time since the last measles vaccination showed no significant waning measles immunity in either child cohort. (E) In contrast, nAb levels waned with age in US adults while they increased in Indian adults

Correlation analysis showed no significant association between nAb titres and time since the last measles vaccination in US or Indian children, indicating no measurable waning (Figure 1D). In adults, due to missing vaccination records in the Indian cohort, we assessed age at enrollment. nAb titres declined with age in US adults (r = −0.16, P = 0.012, Figure 1E), but increased with age in Indian adults (r = 0.21, P < 0.001, Figure 1E).

Our findings reveal notable differences in measles immunity across regions with distinct epidemiological profiles. Although nearly 64% of Indian children received at least three vaccine doses (Supplementary Table S1), their nAb titres were significantly lower than those of US children (Figure 1A). While individual vaccination records were unavailable for the Indian cohorts, the National Immunization Schedule of the Government of India recommends a measles vaccination timeline comparable to that of the USA, with the first dose administered at 9–12 months of age and additional doses at 4–6 years (Supplementary Table S1). Therefore, the observed disparity in nAb titres between two populations suggest that factors beyond vaccine coverage, such as vaccine type, strain, cold chain integrity, nutrition, or health status, and host genetic variation, including polymorphisms in human leukocyte antigen and other immune-related genes, may influence immune responses.⁴ Further investigation into these factors is critical, especially as India has prioritized two-dose coverage to achieve its elimination goal, yet our data demonstrate suboptimal antibody responses even among children who received three doses.

Among adults, nAb titres declined with age in the USA, likely reflecting waning vaccine-derived immunity,⁵ whereas nAb titres increased in Indian adults, likely due to continued viral circulation (Figure 1E). These findings underscore the urgent need for robust serosurveillance and global coordination, particularly in the context of international travel. No country can sustain measles elimination alone.

Our comparative serological data underscore the importance of evaluating not only vaccine coverage, but also vaccine-induced immunity (or lack thereof) within a population. These findings highlight potential immunity gaps and support the need of region-specific vaccination strategies, which are critical for accelerating progress toward global measles elimination, particularly in countries where elimination goals remain unmet. Our study has several limitations. First, the absence of vaccination records in the Indian adult cohort limits our ability to assess nAb kinetics and to distinguish vaccine-induced from infection-induced immunity (Figure 1E). Second, differences in nAb titres among children may be confounded by vaccine type and dosage. As vaccine selection was locally determined and undocumented, future research should explore the mechanisms driving these disparities.

In summary, we observed distinct measles-specific nAb profiles across child and adult cohorts in the USA and India. These findings underscore the urgent need for routine serosurveillance to inform public health policy and advance global measles elimination efforts.

Funding

Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award R01AI121054. The study sponsors have no role in study design, in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Author contributions

Huy Quang Quach (Conceptualization, Data curation, Formal analysis, Investigation, Visualization, Writing—original draft, Writing—review & editing [equal]), Inna G. Ovsyannikova (Methodology, Writing—review & editing [equal]), Gregory A. Poland (Funding acquisition, Methodology, Writing—review & editing [equal]), and Richard Kennedy (Conceptualization, Funding acquisition, Supervision, Writing—review & editing [equal])

Conflict of interest

Dr Poland is the chair of a safety evaluation committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr Poland provides consultative advice to AiZtech; Emergent Biosolutions; GlaxoSmithKline; Merck & Co. Inc.; Moderna; and Syneos Health. Dr Poland holds patents related to vaccinia, influenza, and measles peptide vaccines. Drs. Poland, Kennedy, and Ovsyannikova have received grant funding and royalties from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. Drs Poland, Kennedy, and Ovsyannikova have a pending patent related to COVID-19 peptide-based vaccines. Dr Kennedy also offers consultative advice on vaccine development to Merck & Co. and Sanofi Pasteur. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. Other co-authors declare no competing interests.