Immunogenicity of SARS-CoV-2 vaccines BBV152 (COVAXIN®) and ChAdOx1 nCoV-19 (COVISHIELD™) in seronegative and seropositive individuals in India: a multicentre, nonrandomised observational study.

Background: There are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the age group 18-45 years began in April 2021 when seropositivity rates in the general population were rising due to the delta wave of COVID-19 pandemic during April-May 2021. Methods: Between June 30, 2021, and Jan 28, 2022, we enrolled 691 participants in the age group 18-45 years across four clinical sites in India. In this non-randomised and laboratory blinded study, participants received either two doses of Covaxin® (4 weeks apart) or two doses of Covishield™ (12 weeks apart) as per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titre (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins post two doses. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination. Findings: When compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield™ elicited higher antibody responses than Covaxin® as measured by seroconversion rate (98.3% vs 74.4%, p < 0.0001 in seronegative individuals; 91.7% vs 66.9%, p < 0.0001 in seropositive individuals) as well as by anti-spike antibody levels against the ancestral strain (GMT 1272.1 vs 75.4 binding antibody units/ml [BAU/ml], p < 0.0001 in seronegative individuals; 2089.07 vs 585.7 BAU/ml, p < 0.0001 in seropositive individuals). As participants at all clinical sites were not recruited at the same time, site-specific immunogenicity was impacted by the timing of vaccination relative to the delta and omicron waves. Surrogate neutralising antibody responses against variants-of-concern including delta and omicron was higher in Covishield™ recipients than in Covaxin® recipients; and in seropositive than in seronegative individuals after both vaccination and asymptomatic infection (omicron variant). T cell responses are reported from only one of the four site cohorts where the vaccination schedule preceded the omicron wave. In seronegative individuals, Covishield™ elicited both CD4+ and CD8+ spike-specific cytokine-producing T cells whereas Covaxin® elicited mainly CD4+ spike-specific T cells. Neither vaccine showed significant post-vaccination expansion of spike-specific T cells in seropositive individuals. Interpretation: Covishield™ elicited immune responses of higher magnitude and breadth than Covaxin® in both seronegative individuals and seropositive individuals, across cohorts representing the pre-vaccination immune history of most of the vaccinated Indian population. Funding: Corporate social responsibility (CSR) funding from Hindustan Unilever Limited (HUL) and Unilever India Pvt. Ltd. (UIPL).

Prevention of Micronutrient Deficiencies in Young Children: Consensus Statement from Infant and Young Child Feeding Chapter of Indian Academy of Pediatrics.

JUSTIFICATION: Micronutrient deficiencies have significant impact on the overall health and well-being of society and potential targets for supplementations. It is important to formulate a consensus statement in view of current evidence, and put in place strategies to meet targets. OBJECTIVE: To formulate by endorsement or adoption and disseminate a consensus statement for prevention of micronutrients deficiencies in young children for office practices from an Indian perspective. PROCESS: A National Consultative Meeting was convened by Infant and Young Child Feeding Chapter (IYCF) of Indian Academy of Pediatrics (IAP) on 17 December, 2016 at Mumbai. IYCF chapter, IAP, United Nations Children Fund, National Institute of Nutrition and Government of India were the participating agencies; and participants representing different parts of India were included. CONCLUSIONS: Micronutrient deficiencies are widespread. For its prevention proper maternal and infant-young child feeding strategies need to be practiced. Encourage delayed cord clamping, dietary diversification, germinated foods, soaking and fermentation processes. Existing Iron, Vitamin A, Zinc supplementation and universal salt iodization programs need to be scaled up, especially in high risk groups. Universal vitamin D supplementation need to be in place; though, the dose needs more research. Vitamin B12 deficiency screening and supplementation should be practiced only in high-risk groups. Availability of appropriately fortified foods needs to be addressed urgently.

Infant and Young Child Feeding Guidelines, 2016.

JUSTIFICATION: Shaping up the post-2015 development agenda is of crucial importance in the development process around the Globe as 2015 was the last year of milllionium development goals. It is the right time to asses our own progress vis-a-vis the Millennium Development Goals and these Guidelines are an attempt in that regard. PROCESS: The Infant and Young Child Feeding (IYCF) chapter of Indian Academy of Pediatrics invited a group of experts for National Consultative Meet for discussing and contributing on latest scientific advances and developments. Various partners from WHO, UNICEF, Ministry of Child Welfare Department, Ministry of Health and Family Welfare, Ministry of Chemical and Fertilizers of Govt of India, Human Milk Banking Association (of India), Indian Medico-Legal and Ethics Association (IMLEA), non-governmental organizations and academicians from various states of India contributed to these guidelines. The guidelines were finalized during the IYCNCON 2015 at New Delhi in August 2015. OBJECTIVES: To formulate, endorse, adopt and disseminate guidelines related to Infant and Young Child feeding from an Indian perspective (including human milk banking, infant feeding in the HIV situation, and micro-nutrients). RECOMMENDATIONS: Early initiation of breastfeeding within first hour of birth, exclusive breastfeeding for the first six months followed by continued breastfeeding for up to two years and beyond with appropriate complementary foods after completion of 6 months is the most appropriate feeding strategy. Micro-nutrient supplementation in infants, and adequate nutrition and anemia control for adolescent girls, pregnant and lactating mothers is advocated. Concepts and need for human milk banks in India has also been incorporated.

Influence of maternal vitamin B12 and folate on growth and insulin resistance in the offspring.

The burden of chronic noncommunicable diseases (NCDs) such as diabetes, obesity and cardiovascular disease is shifting rapidly to low- and middle-income countries. It calls for a review of the classic 'dogma' of genetic predisposition, precipitated by adult lifestyle. The paradigm of early life origins of chronic disease has focused attention on maternal health and nutrition as major determinants of the health of the offspring. India has high burden of maternal ill health and also of diabetes and cardiovascular disease, offering unique opportunities to study the links between the two. Pune studies showed that the Indian babies were thin but fat (more adipose) compared to European babies, and that maternal micronutrient status during pregnancy was a determinant of offspring size and body composition. Two thirds of the mothers had low vitamin B12 concentrations, while folate deficiency was rare. Higher circulating concentrations of homocysteine predicted smaller baby size. Follow-up studies revealed that higher maternal folate in pregnancy predicted higher adiposity and insulin resistance in the child at 6 years of age, and that low maternal vitamin B12 exaggerated the risk of insulin resistance. Low maternal vitamin B12 status is also associated with increased risk of neural tube defects and poor offspring cognitive functions. Our results suggest an important role for maternal one-carbon metabolism in offspring growth and programming of NCD risk. These ideas are supported by animal studies. Improvement of adolescent nutrition could effect intergenerational prevention of chronic diseases.

Fetal programming: maternal nutrition and role of one-carbon metabolism.

India is world's capital for low birth weight (LBW), which is ascribed to intrauterine growth restriction (IUGR) rather than prematurity. An average Indian mother is short and thin and gives birth to a light and thin baby. Maternal undernutrition is thought to be a major factor in the aetiology of IUGR, and the undernutrition is usually thought to be a low macronutrient intake. The Pune Maternal Nutrition Study (PMNS) showed that the Indian babies were thin but fat (more adipose) compared to European babies, and that maternal intake of micronutrient-rich foods was a strong determinant of fetal size. Two thirds of the mothers had low vitamin B(12) concentrations, folate deficiency was rare, and high circulating concentrations of homocysteine predicted IUGR. Follow up of these children revealed that higher maternal folate in pregnancy predicted higher adiposity and insulin resistance at 6 years of age. The most insulin resistant children were born to mothers who were vitamin B(12) deficient and had high folate concentrations. Thus, PMNS suggests an important role for maternal one-carbon (1C) metabolism in fetal growth and programming of diabetes risk. This could be due to the role of 1C metabolism in synthesis of nucleic acids, genomic stability and the epigenetic regulation of gene function. In addition, methionine has important role in protein synthesis. These ideas are supported by animal studies. The next logical step in India will be to improve 1C metabolism in adolescents to effect intergenerational prevention of adiposity, diabetes and other related conditions.

Nutrigenetic determinants of neural tube defects in India.

JUSTIFICATION: Neural tube defects (NTDs) are one of the commonest birth defects with a high incidence in India. However, few studies have systematically looked into the etio-pathogeneis of NTDs, which mainly includes nutritional deficiencies and genetic predisposition. Efforts are afoot for universal food fortification with folic acid in the hope of preventing NTDs, without factual evidence of folate deficiency in the target population. EVIDENCE ACQUISITION: We conducted a review of Indian literature on NTDs focusing on the role of folate and vitamin B12 nutrition and common genetic polymorphisms in 1-carbon metabolism. We performed a literature search of Medline and Indian Medlars (www. indmed.nic.in) for articles using following search terms: Neural tube defect and India, published up to November 2008, on human subjects. We did not include individual case reports and case series describing surgical and medical management, genetic syndromes where NTD was only one of the features or unusual associations of NTDs with other clinical findings. RESULTS: Absence of a nationally representative large study, lack of interventional studies and methodological differences were conspicuous during this review. Larger studies are, therefore, urgently needed to delineate genenutrient interactions in association with NTDs in India. We urge that caution should be exercised before widespread folic acid fortification of food, without addressing the issue of concurrent B12 deficiency.

Maternal nutrition, intrauterine programming and consequential risks in the offspring.

It is traditionally believed that genetic susceptibility and adult faulty lifestyle lead to type 2 diabetes, a chronic non-communicable disease. The "Developmental Origins of Health and Disease" (DOHaD) model proposes that the susceptibility to type 2 diabetes originates in the intrauterine life by environmental fetal programming, further exaggerated by rapid childhood growth, i.e. a biphasic nutritional insult. Both fetal under nutrition (sometimes manifested as low birth weight) and over nutrition (the baby of a diabetic mother) increase the risk of future diabetes. The common characteristic of these two types of babies is their high adiposity. An imbalance in nutrition seems to play an important role, and micronutrients seem particularly important. Normal to high maternal folate status coupled with low vitamin B(12) status predicted higher adiposity and insulin resistance in Indian babies. Thus, 1-C (methyl) metabolism seems to play a key role in fetal programming. DOHaD represents a paradigm shift in the model for prevention of the chronic non-communicable diseases.