Abstract
Covishield comprises the larger proportion in the vaccination program in India. Hence, it is of utmost importance to understand neutralizing capability of vaccine against the B.1.617.1 variant which is considered to responsible for surge of the cases in India. The neutralizing-antibody (NAb) titer against B.1.167.1 and prototype B.1 variant (D614G) was determined of the vaccine sera (4 weeks after second dose) of COVID-19 naïve subjects (n=43) and COVID-19 recovered subjects (n=18). The results demonstrated that sera of COVID-19 recovered subjects (n=18) who received two doses of Covishield have higher NAb response compared to the COVID-19 naive with a significant difference (p<0.0001) in NAb titer against B.1 and B.1.617.1 In-spite of reduction in the neutralizing titer against B.1.617.1 variant; Covishield vaccine-induced antibodies are likely to be protective to limit the severity and mortality of the disease in the vaccinated individuals.
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Multiple severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants have emerged and reported from different countries worldwide1. Studies are being conducted on these newly emerging SARS-CoV-2 variants to understand their impact on the efficacy of the currently available COVID-19 vaccines.1 Many of the studies have reported reduced neutralization capabilities of multiple vaccines viz., mRNA-1273, NVX-CoV2373, BNT162b2, BBIBP-CorV, and ChAdOx1-nCoV19 against different variants B.1.1.7, B.1.351 and B.1.1.28 P1.1–2 Recently, new SARS-CoV-2 variant, B.1.617.1, B.1.617.2 and B.1.617.3 with specific deleterious mutations have been reported from India3–4, which has been associated with increase in the number of SARS-CoV-2 cases especially in Maharashtra state3. This variant has been shown to have higher transmissibility and pathogenicity in hamster model and has raised serious concern pertaining to the national COVID-19 vaccination program in India and other countries3,5. Till date, over 170 million doses of vaccine have been administered to Indian citizens with two approved vaccines- Covishield (Astrazeneca-Oxford) and CovaxinTM (BBV152)6. Recently, we have demonstrated the neutralizing efficacy of CovaxinTM against B.1.617.1, B.1.1.7, B.1.1.28.2 and variants.4,7,8 Coviesheild comprises the larger proportion in the vaccination program in India. Hence, it is of utmost importance to understand neutralizing capability of Covishield vaccine against the B.1.617.1 variant in view of the severity of the second wave.
We have evaluated neutralizing capability of the Covishield vaccine using sera obtained from COVID-19 naïve subjects (n=43) and COVID-19 positive recovered subjects (n=18) 4 weeks after the second dose.
The neutralizing-antibody (NAb) titer against B.1.167.1 and prototype B.1 variant (D614G) was determined for both the categories of sera. Of the sera obtained from COVID-19 naïve subjects, 23.25% samples (n=10) didn’t show any NAb titer against both the variants. 27.90% of the samples (n=12) showed NAb titer only with B.1. A total of 21 serum specimens (48.83%) elicited NAb titers against both B.1 and B.1.617.1 variants. The geometrical mean titer (GMT) along with standard deviation of Covishield vaccinee sera against B.1 and B.1.617.1 were 42.92±3.8 (95% CI: 40.21-128.5; n=43) and 21.92±4.42 (95% CI: 24.4-62.64; n=43) respectively.
The results demonstrated that sera of COVID-19 positive recovered subjects (n=18, red color) who received two doses of Covishield have higher antibody response compared to the subjects with COVID-19 naive (n=43, green color) with a significant difference (p <0.0001) in NAb titer against B.1 (triangle) and B.1.617.1 (square) variants (Figure 1 A and 1B). An increase in the GMT of the sera of COVID-19 recovered cases with vaccination (29.5 fold) compared to COVID-19 naïve vaccinees (23.5 fold) was observed against B.1 and B.1.617.1 respectively. This indicates that COVID-19 recovered cases who received 2 doses of vaccine had a better immune response in comparison to COVID-19 naive subjects who receivd 2 doses vaccine.
A pair-wise comparison using Wilcoxon matched-pairs signed-rank test demonstrated a significant two-fold reduction (p-value<0.0001) in the neutralization titer of B.1.617.1 compared to B.1 variant in the COVID-19 naïve vacinees (Figure 1 C). Further, we also determined the IgG titer against S1-RBD and observed a non significant difference between COVID-19 recovered cases administered with 2 dose of vaccine and COVID-19 naive vaccinated cases (Figure 1D).
Inspite of reduction in the neutralizing titer against B.1.617.1 variant; Covishield vaccine-induced antibodies are likely to be protective to limit the severity and mortality of the disease in the vaccinated individuals.
Ethical approval
The study was approved by the Institutional Biosafety Committee and Institutional Human Ethics Committee of ICMR-NIV, Pune, India. under project ‘Propagation of new SRS-CoV-2 variantisolate and characterization in cell culture and animal model.
Author Contributions
PDY and PA contributed to study design, data analysis, interpretation and writing and critical review. GNS, GRD, DYP,RRS, AMS, DAN and SK contributed to data collection, interpretation, writing and critical review. NG, SP, and BB contributed to the critical review and finalization of the paper.
Conflicts of Interest
Authors do not have a conflict of interest among themselves.
Financial support & sponsorship
Financial support was provided by the Indian Council of Medical Research (ICMR), New Delhi at ICMR-National Institute of Virology, Pune under intramural funding ‘COVID-19’.
Acknowledgement
Authors gratefully acknowledge the staff of ICMR-NIV, Pune including Dr. Rajlaxmi Jain, Mr. Prasad Sarkale, Mr. Shrikant Baradkar, Ms. Aasha Salunkhe and Mr. Chetan Patil for extending excellent technical support.