SARS-CoV-2 Delta and Delta AY.1 variant show similar Covaxin-induced neutralization

A new study from India suggests that the Indian-made Covaxin whole-virus inactivated vaccine against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) retains significant efficacy against the newer delta variants of the virus. These preliminary findings come after both variants have shown some resistance to antibody-mediated neutralization elicited by first-generation Pfizer or AstraZeneca coronavirus disease 2019 (COVID-19) vaccines.

A preprint version of the study is available on the bioRxiv* server, while the article undergoes peer review.

Background

COVID-19, caused by the novel SARS-CoV-2 pathogen, has caused immense disruption as governments and public health authorities try to tame it by social distancing, travel bans, lockdowns and vaccination. The unprecedentedly swift development of vaccines and their rapid approval for emergency use has led to well over 600 million doses being distributed worldwide, mostly in the First World.

However, vaccine efficacy is threatened by the emergence of new strains with mutations in the spike region that interacts with the host cell receptor to accomplish infection and viral entry. One such is the delta variant, a SARS-CoV-2 Variant of Concern (VOC) – also known as the B.1.617.2 variant.

First detected in India, it has since been sequenced in many countries, where it has become the dominant strain, passing the sublineages Kappa (B.1.617.1) and B.1.617.3, as well as the earlier alpha, beta and gamma variants.

Recent research indicates that this VOC is susceptible to neutralization by the Pfizer BNT162b2, AstraZeneca Covishield and BBV152/Covaxin vaccines, the latter two being used in India. Nonetheless, the fact remains that the delta variant is responsible for the majority of breakthrough infections worldwide.

The Indian vaccine, BBV152, based on a whole-virion inactivated platform, has successfully passed preclinical and early clinical trials and is being used for mass immunization in the country.

The double-blind, randomized, multicenter, phase 3 clinical trial of this vaccine indicated vaccine efficacy of 65% in terms of protection against the delta variant. Since then, however, further mutations have led to the emergence of Delta AY.1, AY.2, and AY.3.

The AY.1 mutant was also first identified in India, in April 2021, but has now appeared in a score of other countries. It has been reported to have a potential for immune escape. The K417N mutation in the spike protein could confer resistance to monoclonal antibodies Casirivimab and Imdevimab as well.

Researchers are seeking to determine its transmissibility, disease severity and immune escape characteristics. There is little information on its clinical profile in vaccinated individuals.

Study aims

The current study evaluated the titer of the immune antibody isotype immunoglobulin G (IgG) elicited by the vaccine in three test situations.

The researchers examined both IgG and neutralizing antibody levels in three cohorts of subjects. The first included 40 COVID-19-naïve subjects who had been fully vaccinated, the samples being obtained 2.5-22 weeks from the second dose.

The second comprised 20 previously infected subjects who had recovered and taken a full course of the vaccine, collected 14-70 weeks after the second dose. The third consisted of those who had developed breakthrough infections with SARS-CoV-2 after being fully vaccinated, with samples taken at 12-18 weeks from the second dose.

The vaccine used in all cases was BBV152. The geometric mean titer (GMT) of neutralizing antibodies ranged between 200-300 for B.1, delta, and AY.1 strains, but only 165 against B.1.617.3. In the post-COVID-19 vaccinated cohort, it was double or higher for B.1, at approximately 800 vs. 300 in the naïve cohort, but otherwise comparable to those in the first group.

The highest titers were in the breakthrough infection group, at approximately 900 against B.1, and 470, 300 and 260 against the other three variants, respectively.

What were the findings?

The scientists found that neutralizing activity was induced at significantly higher levels by natural infection coupled with vaccination, whether the former occurred prior to or after vaccination. This was confirmed by enzyme-linked immunosorbent assay (ELISA) testing that showed 2.7-4-fold higher titers in the breakthrough cohort relative to the naïve vaccinated cohort when tested for the viral spike S1, receptor-binding domain (RBD) and nucleoprotein.

This may point to the essential role of immune memory cells in boosting the immune response.

Neutralizing activity was reduced slightly, by up to 2-fold, for the Delta, Delta AY.1 and B.1.617.3, relative to the B.1 variant, following full vaccination in naïve individuals. The reduction was greater in the other cohorts, at up to four-fold with the post-COVID-vaccination cases, and 3-5-fold in the third cohort.

With the ChAdOx1 and BNT162b2 vaccines, two doses led to four-fold and 11-fold lower neutralizing titers against the delta variant, as reported in other studies. This has been observed with BBV152 and Covishield as well.

Nonetheless, the researchers observe, “With the observed high titers, the sera of individuals belonging to all the aforementioned groups they would still neutralize the Delta, Delta AY.1 and B.1.617.3 variants effectively.”

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.