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A machine learning-based approach to determine infection status in recipients of BBV152 (Covaxin) whole-virion inactivated SARS-CoV-2 vaccine for serological surveys.

ABSTRACT: Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the vaccine effectiveness. Asymptomatic breakthrough infections have been a major problem in assessing vaccine effectiveness in populations globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines since whole virion vaccines generate antibodies against all the viral proteins. Here, we show how a statistical and machine learning (ML) based approach can be used to discriminate between SARS-CoV-2 infection and immune response to an inactivated whole virion vaccine (BBV152, Covaxin). For this, we assessed serial data on antibodies against Spike and Nucleocapsid antigens, along with age, sex, number of doses taken, and days since last dose, for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, our ensemble ML model classified 724 to be infected. For method validation, we determined the relative ability of a random subset of samples to neutralize Delta versus wild-type strain using a surrogate neutralization assay. We worked on the premise that antibodies generated by a whole virion vaccine would neutralize wild type more efficiently than delta strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, neutralization against Delta strain was more effective, indicating infection. We found 71.8% subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period. Our approach will help in real-world vaccine effectiveness assessments where whole virion vaccines are commonly used.

SUBMITTER: Singh P

PROVIDER: S-EPMC9040372 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceA surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021.ObjectiveTo assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection.Design, setting, and participantsThis was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India.ExposuresVaccination with 0, 1, or 2 doses of BBV152.Main outcomes and measuresThe HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 - adjusted HR) was reported.ResultsAmong 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection.Conclusions and relevanceThese findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.

Project description: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 ∼ Group 2 ∼ 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).

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A machine learning-based approach to determine infection status in recipients of BBV152 (Covaxin) whole-virion inactivated SARS-CoV-2 vaccine for serological surveys.

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