High failure rate of ChAdOx1 in healthcare workers during Delta variant surge: A case for continued use of masks post-vaccination

Abstract

The Oxford-Astra Zeneca COVID 19 vaccine (AZD1222 or ChAdOx1) is an important part of the global vaccine roll-out against SARS-CoV-2, and a locally manufactured version (Covishield by Serum Institute, Pune, India) is the most commonly used vaccine in India. The vaccination program started in January 2021 and here we report effectiveness of the first dose of Covishield in generating antibody response and its kinetics. We further report differences in the quantitative antibody response amongst individuals who had pre-existing antibodies to SARS CoV2 and those who did not. In a group of 135 healthcare workers administered Covishield, we measured antibodies to SARS-CoV-2 directed against the spike protein (S-antigen) using Elecsys Anti-SARS-CoV-2 S quantitative antibody detection kit (Roche Diagnostics) at days 0, 7, 14, and 28. In 44 subjects (32.5%) who had already developed antibodies to SARS-CoV-2 at day 0 (before immunization), it was observed that antibody response was significantly higher at each time point, with the maximum increase seen between days 0 and 7. In contrast the sero-negative group (n=91) started developing antibody response only after 14 days or later. Three sero-negative individuals did not develop any antibody response even at day 28 of vaccination. It is noted that median antibody response at 28 days in seronegative subjects was similar to that of seropositive subjects at baseline (day 0) and was on a rising trajectory. Our data suggests that ChAdOx1 is highly immunogenic, particularly so where previous SARS CoV2 antibody-response is established. Given the high background seropositivity in India, this may be useful in determining optimal timing of the second dose during mass immunization within the constraints of vaccine supply and administration.

SARS-CoV-2 spike E156G/Δ157-158 mutations contribute to increased infectivity and immune escape

“…When the ICS-05/03 spike mutational profile was compared with other spike sequences from the B1 lineages ( Elbe & Buckland-Merrett, 2017 ), they both corresponded to the B.1.617.3 lineage ( Fig 1B ). Notably, the delta variant (B.1.617.2) that dominated the second wave in the country and caused 25.3% of breakthrough infections ( Ujjainiya et al, 2021 Preprint ) shares all spike mutations with B.1.617.3 except T478K ( Fig 1B and C ). The E156G/∆157–158 mutation, first detected on 7 August 2020, subsequently became 35% prevalent worldwide ( Fig 1D ), and by October 2021, it was found in more than 90% of reported sequences from the USA and UK, with a downward trend from India ( Fig 1F ).…”

“…This emergence of variants coincided with the vaccination drive, prioritized for the frontline workers, older population with subsequent rollouts in high-risk groups, and young adults. While the frontline workers mostly received both doses of ChAdOx1 nCoV-19 (Covishield in India) by March 2021, highly transmissible variants such as delta (B.1.617.2) displayed the ability to cause breakthrough infections ( Ujjainiya et al, 2021 Preprint ). Our surveillance analysis also identified cases that were classified as vaccine breakthrough infections, and it became pertinent to understand the potential of the pathogen targeting vaccinated individuals.…”

B.1.617.3 SARS CoV-2 spike E156G/Δ157-158 mutations contribute to reduced neutralization sensitivity and increased infectivity

“…Here, we demonstrated that molecular features of the spike (like L452R and E484Q), already known to confer fitness 7,25,26 , cooperates with alterations in the NTD to enhance spike function further. The now widespread NTD-specific mutation E156G/∆157-158 likely conferred an evolutionary advantage and might underly vaccine breakthroughs found common during the delta outbreaks 5 . One of Delta's siblings, a variant called Lambda that, like Delta, also carries changes in the spike NTD, in addition to L452Q, and these alterations have been linked to the virus' higher infectivity and immune evasion ability 27,28 .…”

“…When the ICS-05 spike sequence was aligned with the available spike sequences on GISAID 15 , it corresponded to the B.1.617 lineage, specifically with B.1.617.3 of the delta variant of concern (Figure -1b). Surfaced in the month of March 2021, the delta variant dominated the second wave in the country (Figure -1c) and was reported to have caused 25.3% of breakthrough infections 5 . The E156G/∆157-158 mutation, first detected on 7 th August 2020, subsequently became 35% prevalent worldwide (Figure -1d), and by August 2021, it was found in more than 85% of reported sequences from the USA, UK, and India (Figure -1f).…”

“…This emergence of variants coincided with the vaccination drive, prioritized for the frontline workers, older population with subsequent rollouts in high-risk groups and young adults. While the frontline workers mostly received both doses of ChAdOx1 nCoV-19 (Covishield TM in India) by March 2021, highly transmissible delta and delta plus variants displayed the ability to cause breakthrough infections, challenging the vaccine efficacy 5 . Our community surveillance analysis also identified a few cases that were classified as vaccine breakthrough infections.…”