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Background In 2016, the Government of India introduced the oral rotavirus vaccine (ROTAVAC, Bharat Biotech, India) in 4 states of India as part of the Universal Immunization Programme, and expanded to 5 more states in 2017. We report four years of data on rotavirus gastroenteritis in hospitalized children < 5 years of age prior to vaccine introduction. Methods Children from 7 sites in southern and northern India hospitalized for diarrhoea were recruited between July 2012 and June 2016. Stool samples were screened for rotavirus using enzyme immunoassay (EIA). The EIA positive samples were genotyped by reverse-transcription polymerase chain reaction. Results Of the 5834 samples from the 7 sites, 2069 (35.5%) were positive for rotavirus by EIA. Genotyping was performed for 2010 (97.1%) samples. G1P[8](56.3%), G2P[4](9.1%), G9P[4](7.6%), G9P[8](4.2%), and G12P[6](3.7%) were the common genotypes in southern India and G1P[8](36%), G9P[4](11.4%), G2P[4](11.2%), G12P[6](8.4%), and G3P[8](5.9%) in northern India. Conclusions The study highlights the high prevalence of rotavirus gastroenteritis in India and the diversity of rotavirus genotypes across different geographical regions. Pre- vaccine surveillance data is necessary to evaluate the potential change in admission rates for gastroenteritis and circulating rotavirus genotypes after vaccine introduction, thus assessing impact.

Multiple severe acute respiratory syndrome (SARS-CoV-2) exposures either due to infection or vaccination result in differential immune responses. Limited data exist on community-level SARS-CoV-2 variant exposures in India. We assessed antibody levels in 211 unvaccinated and 349 vaccinated individuals with and without prior exposure, followed for ~ 2 years (May 2021–October 2023) with baseline blood, weekly saliva for RT-PCR, and blood draws at ~ 6, 12, and 24 months. Humoral and cellular immune responses following primary ( N  = 8) and secondary ( N  = 11) Omicron infections in unvaccinated, previously exposed ( N  = 25), and unexposed vaccinated ( N  = 14) individuals were evaluated using Meso Scale Discovery and flow cytometry assays at Day 0, 30, and 90. Previously exposed individuals had higher anti-spike IgG levels at baseline (median 57,732 vs. 11,359, p  < 0.001 in unvaccinated; 93,827 vs. 26,883, p  < 0.001 in vaccinated) and 99% seropositivity at 2 years. Secondary Omicron infection elicited higher anti-spike IgG levels (17,320 vs. 3,930, p  < 0.01) and stronger CD8 T cell responses (median CD8 AIM 0.026 vs. 0.001, p  = 0.01 at Day90) than primary Omicron infection. Vaccinated individuals showed comparable CD4 and CD8 T cell responses irrespective of prior exposure, but previously exposed individuals had more durable antibodies at Day90 ( p  < 0.05 in previously exposed). Anti-spike IgG levels and %ACE-2 inhibition to Omicron were lower in both groups compared to other variants. High seropositivity was observed in both vaccinated and unvaccinated individuals after multiple exposures, though antibody levels were higher in individuals with prior exposure. These findings underscore preserved T cell responses to Omicron, although with lesser magnitude among unvaccinated.

Rotavirus infection is a cause of considerable morbidity, with an estimated 500,000 deaths annually worldwide. This study in Vellore, India, showed that recurrent rotavirus infection in children was common, often with the same serotype. Group A rotaviruses are the leading cause of dehydrating gastroenteritis in young children worldwide, and rotavirus gastroenteritis results in more than half a million deaths annually. 1 Two rotavirus vaccines, Rotarix and RotaTeq, are licensed for use in the United States, Europe, and Latin America, 2 – 4 and the World Health Organization has recommended their inclusion in national immunization programs in Africa and Asia on the basis of trials showing efficacy there. 5 , 6 Naturally occurring rotavirus infection has been shown to confer protection against subsequent infection and disease in birth cohorts in Mexico and Guinea-Bissau, with each new infection reducing the severity . . .

Interference from transplacental and breast milk antibodies may impede the performance of oral live vaccines. The effect of breastfeeding on the immunogenicity of Rotarix®, a two-dose oral monovalent rotavirus vaccine, was examined in a community-based trial in New Delhi, India. Four hundred mother–infant pairs were randomized into two equal groups. Infants were aged 6–7 weeks at enrollment. Mothers were encouraged to either breastfeed or to withhold breastfeeding during the 30min prior to and after each vaccine dose was administered. We collected blood specimens from infants at enrollment and 4 weeks after the second vaccine dose. Blood and breast milk specimens were obtained from mothers at baseline and breast milk specimens were collected at the time of the second vaccine dose. Seroconversion was defined as infant serum anti-VP6 IgA antibody level of ≥20IU/mL 4 weeks after the second vaccine dose and a ≥4-fold rise from baseline. There was no difference in the proportion who seroconverted between the two groups (26% vs 27%; p=0.92). The levels of infant serum IgA, maternal serum and breast milk IgA and IgG anti-rotavirus antibodies predicted the anti-rotavirus IgA level in infants at end-study and explained approximately 10% of the variability of the immune response (r2=0.10, p<0.001). In this population, the immune response to Rotarix® was not enhanced by withholding breastfeeding around the time of vaccination. Maternal anti-rotavirus antibodies explained little of the variability in the immune response to the vaccine. Factors other than maternal anti-rotavirus antibodies probably explain why infants in low-and middle-income settings respond poorly to live oral rotavirus vaccines.

This proof-of-concept study tested if prior BCG revaccination can qualitatively and quantitively enhance antibody and T-cell responses induced by Oxford/AstraZeneca ChAdOx1nCoV-19 or COVISHIELD™, an efficacious and the most widely distributed vaccine in India. We compared COVISHIELD™ induced longitudinal immune responses in 21 BCG re-vaccinees (BCG-RV) and 13 BCG-non-revaccinees (BCG-NRV), all of whom were BCG vaccinated at birth; latent tuberculosis negative and SARS-CoV-2 seronegative prior to COVISHIELD™ vaccination. Compared to BCG-NRV, BCG-RV displayed significantly higher and persistent spike-specific neutralizing (n) Ab titers and polyfunctional CD4+ and CD8+ T-cells for eight months post COVISHIELD™ booster, including distinct CD4+IFN-γ+ and CD4+IFN-γ- effector memory (EM) subsets co-expressing IL-2, TNF-α and activation induced markers (AIM) CD154/CD137 as well as CD8+IFN-γ+ EM,TEMRA (T cell EM expressing RA) subset combinations co-expressing TNF-α and AIM CD137/CD69. Additionally, elevated nAb and T-cell responses to the Delta mutant in BCG-RV highlighted greater immune response breadth. Mechanistically, these BCG adjuvant effects were associated with elevated markers of trained immunity, including higher IL-1β and TNF-α expression in CD14+HLA-DR+monocytes and changes in chromatin accessibility highlighting BCG-induced epigenetic changes. This study provides first in-depth analysis of both antibody and memory T-cell responses induced by COVISHIELD™ in SARS-CoV-2 seronegative young adults in India with strong evidence of a BCG-induced booster effect and therefore a rational basis to validate BCG, a low-cost and globally available vaccine, as an adjuvant to enhance heterologous adaptive immune responses to current and emerging COVID-19 vaccines.

Launched in 1974, the Expanded Program on Immunization (EPI) is estimated to prevent two-three million deaths annually from polio, diphtheria, tuberculosis, pertussis, measles, and tetanus. Additional lives could be saved through better understanding what influences adherence to the EPI schedule in specific settings. The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study followed cohorts in eight sites in South Asia, Africa, and South America and monitored vaccine receipt over the first two years of life for the children enrolled in the study. Vaccination histories were obtained monthly from vaccination cards, local clinic records and/or caregiver reports. Vaccination histories were compared against the prescribed EPI schedules for each country, and coverage rates were examined in relation to the timing of vaccination. The influence of socioeconomic factors on vaccine timing and coverage was also considered. Coverage rates for EPI vaccines varied between sites and by type of vaccine; overall, coverage was highest in the Nepal and Bangladesh sites and lowest in the Tanzania and Brazil sites. Bacillus Calmette-Guérin coverage was high across all sites, 87–100%, whereas measles vaccination rates ranged widely, 73–100%. Significant delays between the scheduled administration age and actual vaccination date were present in all sites, especially for measles vaccine where less than 40% were administered on schedule. A range of socioeconomic factors were significantly associated with vaccination status in study children but these results were largely site-specific. Our findings highlight the need to improve measles vaccination rates and reduce delayed vaccination to achieve EPI targets related to the establishment of herd immunity and reduction in disease transmission.

Oral poliovirus vaccine is less immunogenic and effective in low-income countries than in high-income countries, similarly to other oral vaccines. The high prevalence of intestinal pathogens and associated environmental enteropathy has been proposed to explain this problem. Because administration of an antibiotic has the potential to resolve environmental enteropathy and clear bacterial pathogens, we aimed to assess whether antibiotics would improve oral poliovirus vaccine immunogenicity. We did a double-blind, randomised, placebo-controlled trial of the effect of azithromycin on the immunogenicity of serotype-3 monovalent oral poliovirus vaccine given to healthy infants living in 14 blocks of Vellore district, India. Infants were eligible to participate if they were 6–11 months old, available for the study duration, and lacked serum neutralising antibodies to serotype-3 poliovirus. Infants were randomly assigned (1:1) at enrolment to receive oral 10 mg/kg azithromycin or placebo once daily for 3 days, followed by serotype-3 monovalent oral poliovirus vaccine on day 14. The primary outcome was detection of serum neutralising antibodies to serotype-3 poliovirus at a dilution of one in eight or more on day 35 and was assessed in the per-protocol population (ie, all those who received azithromycin or placebo, oral poliovirus vaccine, and provided a blood sample according to the study protocol). Safety outcomes were assessed in all infants enrolled in the study. The trial is registered with the Clinical Trials Registry India, number CTRI/2014/05/004588. Between Aug 5, 2014, and March 21, 2015, 754 infants were randomly assigned: 376 to receive azithromycin and 378 to placebo. Of these, 348 (93%) of 376 in the azithromycin group and 357 (94%) of 378 infants in the placebo group completed the study per protocol. In the azithromycin group, 175 (50%) seroconverted to serotype-3 poliovirus compared with 192 (54%) in the placebo group (risk ratio 0·94, 95% CI 0·81–1·08; p=0·366). Azithromycin reduced faecal biomarkers of environmental enteropathy (calprotectin, myeloperoxidase, α1-antitrypsin) and the prevalence of bacterial but not viral or eukaryotic pathogens. Viral pathogens were associated with lower seroconversion. Three serious adverse events were reported (two in the azithromycin group and one in the placebo group), but none was considered related to the study interventions. Azithromycin did not improve the immunogenicity of oral poliovirus vaccine despite reducing biomarkers of environmental enteropathy and the prevalence of pathogenic intestinal bacteria. Viral interference and innate antiviral immune mechanisms might be more important determinants of the immunogenicity of live-virus oral vaccines. Bill & Melinda Gates Foundation.

Background Stunting in developing countries continues to be a major public health problem. Measuring head circumference (HC) during clinical anthropometric assessment can help predict stunting. The aim of this study was to assess burden and determine the predictors of low HC (<− 2 SD) at birth and during first 2 years of life in a semi- urban settlement of Vellore. Methods The study uses baseline data and serial HC measurements from the birth cohort of MAL-ED study, where 228 children from Vellore completed follow-up between March 2010 to February 2014. Analysis of baseline, maternal and paternal characteristics, micro-nutrient status and cognition with HC measurements was performed using STATA version 13.0 software. Results The mean HC (±SD) at 1st, 12th and 24th month were 33.37 (1.29) cm, 42.76 (1.23) cm and 44.9 (1.22) cm respectively. A third of the infants (75/228) had HC less than − 2 SD at first month of life, and on follow-up, 50% of the cohort had HC ≤ -2 SD both at 12th and 24th month. Low HC measurements at all three time-points were observed for 21.6% (46/222) infants. Low HC was significantly associated with stunting in 37.3% (OR = 10.8), 57.3% (OR = 3.1) and 44.4% (OR = 2.6) children at 1st, 12th and 24th month respectively. Bivariate analysis of low HC (<− 2 SD) at 12th month showed a statistically significant association with lower socioeconomic status, low paternal and maternal HC and low maternal IQ. Multivariable logistic regression analysis showed maternal (AOR = 0.759, 95% CI = 0.604 to 0.954) and paternal (AOR = 0.734, 95% CI = 0.581 to 0.930) HC to be significantly associated with HC attained by the infant at the end of 12 months. Conclusions One-third of the children in our cohort had low head circumference (HC) at birth, with one-fifth recording low HC at all time-points until 2 years of age. Low HC was significantly associated with stunting. Paternal and maternal HC predicted HC in children. HC measurement, often less used, can be a simple tool that can be additionally used by clinicians as well as parents/caregivers to monitor child growth.

IntroductionThe incidence of SARS-CoV-2 re-infection has not been widely evaluated in low-income and middle-income countries. Understanding immune responses elicited by SARS-CoV-2 natural infection and factors that lead to re-infection in a community setting is important for public health policy. We aim to investigate the risk of primary infection and re-infection among those without and with evidence of prior infection as defined by the presence of antibodies to SARS-CoV-2 spike protein.Methods and analysisA baseline seroprevalence survey will test for SARS-CoV-2 antibodies among healthy adults in Vellore, India. Based on an expected seropositivity rate of 50% in the general population, with annual attack rates of 12%, 6%, 4.8% and 4% among those unvaccinated and seronegative, vaccinated and seronegative, unvaccinated and seropositive, and vaccinated and seropositive, respectively, we will recruit 1200 adults who will be followed up for a total of 24 months. Weekly self-collected saliva samples will be tested by reverse transcription-PCR (RT-PCR) to detect SARS-CoV-2 infections, for a period of 1 year. For any person testing RT-PCR positive, blood samples will be collected within 2 days of RT-PCR positivity and on days 30 and 90 to assess the kinetics and longevity of the antibody responses, B cell memory and T cell memory post-infection. The data will be analysed to estimate seroprevalence at baseline and over time, the risk factors for infection, rates of primary infection and re-infection, and provide a comparison of the rates across groups based on infection and vaccination status.Ethics and disseminationThe study has been approved by the Institutional Review Board (IRB No: 13585) of Christian Medical College and Hospital, Vellore. The results of the study will be made available through journal publications and conference presentations.Trial registration numberCentral Trial Registry of India: CTRI/2020/11/029438.

Detailed characterisation of immune responses induced by COVID-19 vaccines rolled out in India: COVISHIELDTM (CS) and COVAXIN® (CO) in a pre-exposed population is only recently being discovered. We addressed this issue in subjects who received their primary series of vaccination between November 2021 and January 2022. Both vaccines are capable of strongly boosting Wuhan Spike-specific neutralising antibody, polyfunctional Th1 cytokine producing CD4+ T-cells and single IFN-γ + CD8+ T-cells. Consistent with inherent differences in vaccine platform, the vector-based CS vaccine-induced immunity was of greater magnitude, breadth, targeting Delta and Omicron variants compared to the whole-virion inactivated vaccine CO, with CS vaccinees showing persistent CD8+ T-cells responses until 3 months post primary vaccination. This study provides detailed evidence on the magnitude and quality of CS and CO vaccine induced responses in subjects with pre-existing SARS-CoV-2 immunity in India, thereby mitigating vaccine hesitancy arguments in such a population, which remains a global health challenge.