key: cord-0821381-gddc8ato authors: Das, S.; Singh, J.; Shaman, H.; Singh, B.; Anantharaj, A.; Sharanabasava, P.; Pandey, R.; Lodha, R.; Pandey, A. K.; Medigeshi, G. R. title: Antibody response after a single dose of BBV152 vaccine negatively correlates with pre-existing antibodies and induces a significant but low levels of neutralizing antibodies to Omicron variant date: 2022-02-08 journal: nan DOI: 10.1101/2022.02.07.22270612 sha: feedbd9a92f05661dfe7ceee0f48a2bc3a773c2a doc_id: 821381 cord_uid: gddc8ato Most adults in India have received at least one dose of COVID-19 vaccine and also been infected naturally during the pandemic. As immunization of individuals continues under this situation where the virus has attained endemicity, we assessed whether this hybrid immunity is further boosted by a single dose of BBV152, an inactivated SARS-CoV-2 vaccine, and, if these antibodies can neutralize SARS-CoV-2 delta and omicron variants. We found that natural infection during the second wave in 2021 led to generation of neutralizing antibodies against other lineages of SARS-CoV-2 including the omicron variant, albeit at a significantly lower level for the latter. A single dose of BBV152 boosted antibody titers against the delta and the omicron variants but the antibody levels remained low for the omicron variant. Boosting of antibodies showed negative correlation with baseline neutralizing antibody titers suggesting anergy of the immune system in individuals with high levels of antibodies. this situation where the virus has attained endemicity, we assessed whether this hybrid 27 immunity is further boosted by a single dose of BBV152, an inactivated SARS-CoV-2 28 vaccine, and, if these antibodies can neutralize SARS-CoV-2 delta and omicron variants. 29 We found that natural infection during the second wave in 2021 led to generation of CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 8, 2022. ; https://doi.org/10.1101/2022.02.07.22270612 doi: medRxiv preprint 40 Serosurveillance studies have showed that 69% of the Indian population had antibodies 41 for COVID-19 after the second wave 1 and a subsequent serosurvey from Delhi showed 42 seropositivity of over 90% 2 suggesting that India was/is a heterogenous mix of people 43 with immunity to COVID-19 due to vaccination or natural infection or both after the second 44 wave. As COVID-19 has attained a state of endemicity and majority of the population got of concern as compared to delta and ancestral virus. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. incubated at RT (232C) for 30 ± 10 min. Substrate was added and OD was recorded 129 and data was analyzed as described in the previous section. The assay has a limit of 130 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Figure 1E ). While this study was in progress, omicron (B.1.1.529) emerged as a variant of 198 concern and antibodies from most vaccines showed reduced efficiency in neutralizing this 199 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. in other studies 13-15 . In naturally infected individuals, boosting after six months is predicted 214 to increase the vaccine effectiveness against variants of concern 16 . We were not able to 215 ascertain the exact date of past infection in most of these individuals which is not unusual 216 as most COVID-19 infections are asymptomatic or mild and are not diagnosed. Nucleocapsid antibodies are known to decay with a half-life of 68 days 17 and 59% of our 218 study participants were positive for N antibodies suggesting that they could have been 219 infected with SARS-CoV-2 within the past 6-8 months. Therefore, we cannot rule out the 220 possibility that some of the subjects with high antibody titers were in their early 221 convalescence and therefore, the boosting effect may not have been significant due to 222 . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. We thank all the members of the bioassay lab for technical support. We thank Neha Garg 246 and Shamsher Singh for data management. We thank all the participants who consented 247 to enrol into the study. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 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The copyright holder for this preprint this version posted February 8, 2022. ; https://doi.org/10.1101/2022.02.07.22270612 doi: medRxiv preprint . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted February 8, 2022. ; https://doi.org/10.1101/2022.02.07.22270612 doi: medRxiv preprint