Polyfunctional CD4 T-cells correlating with neutralising antibody is a hallmark of COVISHIELDTM and COVAXIN® induced immunity in COVID-19 exposed Indians.

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.

Characterization of immune responses to two and three doses of the adenoviral vectored vaccine ChAdOx1 nCov-19 and the whole virion inactivated vaccine BBV152 in a mix-and-match study in India.

Infections with SARS-CoV-2 variants and declining immunity after primary vaccination, encouraged the use of booster doses. Some countries changed their immunization programmes to boost with vaccines different from the ones in their original schedule, based on results from immunogenicity and effectiveness studies. This study reports immunological analysis of samples collected in a phase 4 randomized trial, where participants who had previously received two primary doses of ChAdOx1 nCov-19 (ChAd) or inactivated BBV152 vaccine were randomized to receive either ChAd or BBV152 booster and further categorized as: Group 1 (two primary doses of ChAd - ChAd booster), Group 2 (two primary doses of ChAd - BBV152 booster), Group 3 (two primary doses of BBV152 - ChAd booster), and Group 4 (two primary doses of BBV152 - BBV152 booster). SARS-CoV-2 specific cellular and humoral responses at day 0 (pre-boost samples 12-36 weeks after the second primary dose), and at day 28 post booster, were measured in a subset of participants (ChAd recipients, n = 37 and BBV152 recipients, n = 36). Additionally, on day180 post-booster humoral responses were assessed for the entire cohort (N = 378). Primary vaccination with 2 doses of BBV152 generated higher memory-B cells (median% 0.41 vs 0.35) and cytokine producing CD8-Tcells (median% 0.09 vs 0.04) while lower anti-spike IgG levels (medianAU/ml: 12,433 vs 27,074) as compared to ChAd. Irrespective of the primary vaccine received, ChAd boosted individuals generated higher memory-B cell frequencies and anti-spike IgG levels as compared to BBV152 booster. The percentage ACE-2 inhibition against Omicron and its sub-variants was higher in Group 3 (median > 60 %) as compared to other groups (median < 25 %). At day180 post booster the hierarchy of the antibody amounts was Group 1 âˆ¼ Group 2 âˆ¼ Group 3 > Group 4. Sustained humoral and robust cellular immune response to SARS-CoV-2 can be obtained with ChAd booster irrespective of the primary vaccination regimen. The trial is registered with ISRTCN (CTRI/2021/08/035648).

Immunogenicity and safety of homologous and heterologous booster vaccination of ChAdOx1 nCoV-19 (COVISHIELD™) and BBV152 (COVAXIN®): a non-inferiority phase 4, participant and observer-blinded, randomised study.

Background: Primary SARS-CoV-2 vaccination has been shown to wane with time and provide lower protection from disease with new viral variants, prompting the WHO to recommend the administration of booster doses. We determined the safety and immunogenicity of homologous or heterologous boosters with ChAdOx1 nCoV-19 (COVISHIELD™) or BBV152 (COVAXIN®), the two vaccines used widely for primary immunization in India, in participants who had already received two primary doses of these vaccines. Methods: Participants primed with two doses each of COVISHIELD™ or COVAXIN® 12-36 weeks previously, were randomised to receive either COVISHIELD™ or COVAXIN® booster in a 1:1 ratio. The primary outcome was day 28 post-booster anti-spike IgG seropositivity and secondary outcomes were anti-spike IgG levels and assessment of safety and reactogenicity. The results of 90 days intention-to-treat analysis are presented. This trial is registered with ISRCTN (CTRI/2021/08/035648). Findings: In the COVISHIELD™ primed group with 200 participants, the seropositivity 28 days post booster in the heterologous COVAXIN® arm was 99% and non-inferior to the homologous COVISHIELD™ arm, which was also 99% (difference 0%; 95% CI: -2.8% to 2.7%). The geometric mean concentration (GMC) of anti-spike antibodies following heterologous COVAXIN® boost on day 28 was 36,190.78 AU/mL (95% CI: 30,526.64-42,905.88) while the GMC following homologous COVISHIELD™ boost was 97,445.09 AU/mL (82,626.97-114,920.7). In the COVAXIN® primed group with 204 participants, the seropositivity 28 days post booster in the heterologous COVISHIELD™ arm was 100% and non inferior to the homologous COVAXIN® arm which was 96% (difference 4%, 95% CI: 0.2%-7.8%). The GMC following heterologous COVISHIELD™ boost was 241,681.6 AU/mL (95% CI: 201,380.2-290,048.3) compared to homologous COVAXIN® boost, which was 48,473.94 AU/mL (95% CI: 38,529.56-60,984.95). The day 28 geometric mean ratio (GMR) of the anti-spike IgG between the heterologous and homologous boosted arms was 0.42 (95% CI: 0.34-0.52) in the COVISHIELD™ primed group and 5.11 (95% CI: 3.83-6.81) in the COVAXIN® primed group. There were no related serious adverse events reported in any group. Interpretation: Homologous and heterologous boosting with COVISHIELD™ or COVAXIN® in COVISHIELD™ or COVAXIN® primed individuals are immunogenic and safe. A heterologous boost with COVISHIELD™ after COVAXIN® prime offers the best immune response among the four combinations evaluated. Funding: Azim Premji Foundation and Bill and Melinda Gates Foundation.

Risk of COVID-19 re-infection and its predictors (CORES): protocol for a community-based longitudinal cohort study in Vellore, India.

INTRODUCTION: The 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 ANALYSIS: A 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 DISSEMINATION: The 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 NUMBER: Central Trial Registry of India: CTRI/2020/11/029438.