Hybrid immunity shown to offer sub-optimal protection against SARS-CoV-2 Omicron variant

In a recent study published on the medRxiv* pre-print server, researchers tested the ability of vaccine, and vaccine and natural infection-induced immunity to neutralize the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant.

After India witnessed a massive surge in coronavirus disease 2019 (COVID-19) cases due to the Delta (B.1.617.2) variant during April-May 2021, a serosurvey showed an immunoglobulin G (IgG) antibody prevalence rate of 69.2% in the COVID-19-infected population. Although preliminary reports have suggested that the Omicron variant is significantly less susceptible to in vitro neutralization by antibodies among recipients of BBV152 (Covaxin, Bharat Biotech) and ChAdOx1nCoV-19 (Covishield, Serum Institute of India) vaccines, data for individuals naturally infected and COVID-19 vaccinated is sparsely available.

About the study 

In the present study, researchers evaluated the neutralizing power of the vaccine and vaccine plus infection-induced antibodies against the Omicron variant in a live virus neutralization assay. The authors randomly sampled Covishield and Covaxin vaccine recipients from the COVID-19 research cohort developed by Translational Health Science and Technology Institute, Faridabad, India. The 80 consenting subjects included in the current study were divided into four groups of 20 participants each.

The participants of the first set of two groups were vaccinated with two doses of the Covishield or Covaxin, and that of the other set of two groups were vaccinated with two doses of the same vaccines (Covishield or Covaxin) and had RT-PCR confirmed prior SARS-CoV-2 infection. The median age of the participants was 58 years, with 47% of participants over 60 years of age. The time elapsed after complete vaccination and natural infection during the study was around seven months.

Results

In the population serosurvey, the detection of anti-RBD IgG antibodies reflects past infection. IgG antibodies induced by the BBV152 vaccine (Covaxin) were detected in 8 out of 20 participants in the BBV152 vaccination group alone as these antibodies start waning in ~6 months post-vaccination. A total of 18 out of 20 participants of the BBV152 vaccination plus infection group had IgG antibodies compared to 11 of 20 ChAdOx1 nCoV-19 (Covishield) vaccination plus infection group, suggesting boosted IgG response after infection in individuals vaccinated with Covaxin.

For this analysis, a neutralization geometric mean titer (GMT) of 1:20 or more was 'protective'. The study findings, thus, showed a fewer proportion of neutralizing antibodies with FRNT50 titers greater than 1:20 against the Omicron variant, compared to the WT strain and the Delta variant.

Compared to the wild-type (WT) virus, in all the four groups, the GMT showed a 2.2 to 3.4-fold reduction against the Delta variant. However, the GMT showed a 25- to 27-fold and a 52- to 54-fold reduction against the Omicron variant in the vaccinated and hybrid immunity groups, respectively, compared to the ancestral strain. While the Delta variant-induced infection increased neutralizing titers against the WT virus, increasing GMT values from 384 to 795 in the BBV152-vaccinated group, and from 383 to 1424 in the ChAdOx1 group led to a decreased neutralizing titers against the Omicron variant. 

As expected, subjects infected with SARS-CoV-2 post-vaccination showed an increase in titers against the Delta variant in the BBV152 and ChAdOx1 nCoV-19 vaccinated groups. The GMT for the Delta variant increased from 174 to 318 and from 111 to 451 in the BBV152 and the ChAdOx1 nCoV-19 vaccination groups, respectively. 

The type of vaccine did not influence the neutralization titer in the present study, more specifically against the Omicron variant. However, the neutralization titers for the Omicron were better among those vaccinated with the Covishield vaccine and who had a previous SARS-CoV-2 infection.

Overall, these study findings suggest that recipients of both Covaxin and Covishield vaccines had a significantly reduced in vitro neutralization against the Omicron variant regardless of the past infection with SARS-CoV-2.

Conclusions 

In the present study, the fold reduction against the Omicron variant in the neutralizing ability of vaccinated and hybrid immunity groups was mainly due to a significant increase in the serum IgG antibodies titers primarily generated against the WT SARS-CoV-2 strain. Since Omicron has a much different RBD with 30 substitutions in its spike (S) protein, it was expected that serum IgG antibody titers against Omicron would be reduced. Therefore, while the fold change showing high reduction compared to the WT might be misleading, the percentage of people with vaccinated/hybrid immunity neutralizing the Omicron variant at that GMT is an important finding.

Further, the study participants who were tested for their IgG serum levels after six months from their second dose demonstrated a marginally better neutralization potential against the Omicron. While neutralizing antibodies prevents SARS-CoV-2 infection, host-induced CD4+ and CD8+ T-cell immune response is also an important defense mechanism against the Omicron variant. Several past studies have shown that the T cell response against the S proteins of most of the variants, including Omicron, offers protection despite the decreased neutralizing ability of the vaccinated plasma.

The final impact on the hospitalization and mortality rates of the Omicron variant-led infections also depends on Omicron's inherent pathogenicity, the host's innate and cellular immune responses, and epidemiological factors such as the proportion of individuals who might have a hybrid immunity from a vaccine and past infection.

As indicated by the study findings, except for immune evasiveness, the other factors favored a reduced incidence of severe COVID-19 from the Omicron-led surge, compared to the previous surge. Furthermore, the researchers recommended an additional third dose of vaccine to augment antibody response against the Omicron variant in vulnerable people after six months of vaccination or natural infection.

*Important notice

medRxiv 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

Neha Mathur

Neha Mathur has a Master’s degree in Biotechnology and extensive experience in digital marketing. She is passionate about reading and music. When she is not working, Neha likes to cook and travel.