Warner, Nathaniel D.

ImportanceIndia’s goal of measles elimination remains unmet, as evidenced by significant recent outbreaks.ObjectiveTo identify seroprevalence rates among vaccinated children and to examine demographic factors that influence antibody responses.Design, Setting, and ParticipantsThis 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.ExposureMeasles-specific antibodies were quantified in serum samples.Main Outcomes and MeasuresMeasles-specific immunoglobulin G (IgG) and neutralizing antibodies were quantified in both children and mothers. Measles-specific IgM was also measured in children.ResultsThe 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 RelevanceIn 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.

As an extremely contagious pathogen, a high rate of vaccine coverage and the durability of vaccine-induced immunity are key factors to control and eliminate measles. Herein, we assessed the seroprevalence of antibodies specific to measles in a cohort of 1393 adults (20–44 years old). ELISA results showed a nontrivial proportion of 37.6% study subjects being negative for measles immunoglobulin G (IgG). We also found significant influences of sex and age of the study cohort on the IgG level. Our findings suggest that even within a highly vaccinated population, a subset of individuals may still have sub-optimal immunity against measles and potentially be susceptible during any future measles outbreaks.

AbstractBackgroundA third dose of measles-mumps-rubella vaccine (MMR3) is recommended in mumps outbreak scenarios, but the immune response and the need for widespread use of MMR3 remain uncertain. Herein, we characterized measles-specific immune responses to MMR3 in a cohort of 232 healthy subjects.MethodsSerum and peripheral blood mononuclear cells (PBMCs) were sampled at day 0 and day 28 after MMR3. Measles-specific binding and neutralizing antibodies were quantified in sera by enzyme-linked immunosorbent assay and a microneutralization assay, respectively. PBMCs were stimulated with inactivated measles virus, and the release of cytokines/chemokines was assessed by a multiplex assay. Demographic variables of subjects were examined for potential correlations with immune outcomes.ResultsOf the study participants, 95.69% and 100% were seropositive at day 0 and day 28, respectively. Antibody avidity significantly increased from 38.08% at day 0 to 42.8% at day 28 (P = .00026). Neutralizing antibodies were significantly enhanced, from 928.7 at day 0 to 1289.64 mIU/mL at day 28 (P = .0001). Meanwhile, cytokine/chemokine responses remained largely unchanged. Body mass index was significantly correlated with the levels of inflammatory cytokines/chemokines.ConclusionsMeasles-specific humoral immune responses, but not cellular responses, were enhanced after MMR3 receipt, extending current understanding of immune responses to MMR3 and supporting MMR3 administration to seronegative or high-risk individuals.

We tested the hypothesis that dietary Na + intake alters the hemodynamic response to mental stress (MS) in normotensive subjects, which could be mediated by β‐adrenergic receptors (ADRB). As part of an ongoing ADRB2 phenotyping protocol, 12 subjects (age 23±5 year) completed 5 days of low (10 mmol day −1 ), normal (150) and high (400) dietary Na + intake. We measured heart rate (ECG), mean arterial pressure (MAP, Finometer), and calculated stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR) responses to arithmetic MS, before and after administration of propranolol. The high Na + diet decreased CO (6.3±0.3 vs. 5.7±0.3 l min −1 , p<0.01) and increased SVR (1187±47 vs. 1311±68 dynes s −1 cm −1 , p<0.01) at rest, but MAP was unchanged (92±2 vs. 93±3 mmHg, p=0.37). During MS, the increase in HR, CO, and MAP was not affected by diet, nor was the decrease in SVR. However, on the high Na + diet β‐blockade increased resting MAP (93±3 vs. 97±2 mmHg, p<0.01), while the absolute MAP response to MS was unchanged, the ΔMAP was blunted (7.3 vs. 4.3 %, p=0.03) and ΔSV was decreased (1.7±3.5 vs. −5.3±2.0 %, p=0.03). In conclusion, reactivity to MS was not influenced by dietary Na + , but systemic β‐blockade after high Na + blunted the SV response during MS. This may be suggestive of augmented ADRB function or blunted non‐ADRB mechanisms of ventricular function during MS after high Na + . Support: R‐01 HL‐089331 and CTSA RR‐024150.

Introduction: Comprehensive evaluation of measles-specific humoral immunity after vaccination is important for determining new and/or additional correlates of vaccine immunogenicity and efficacy. Methods: We used a novel proteome microarray technology and statistical modeling to identify factors and models associated with measles-specific functional protective immunity in 150 measles vaccine recipients representing the extremes of neutralizing antibody response after two vaccine doses. Results: Our findings demonstrate a high seroprevalence of antibodies directed to the measles virus (MV) phosphoprotein (P), nucleoprotein (N), as well as antibodies to the large polymerase (L) protein (fragment 1234 to 1900 AA). Antibodies to these proteins, in addition to anti-F antibodies (and, to a lesser extent, anti-H antibodies), were correlated with neutralizing antibody titer and/or were associated with and predictive of neutralizing antibody response. Conclusion: Our results identify antibodies to specific measles virus proteins and statistical models for monitoring and assessment of measles-specific functional protective immunity in vaccinated individuals.