COVID-19 recovered vaccinated individuals more protected from Delta variant

The B.1.617 lineage of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in October 2020, has led to new outbreaks of the infection and new waves of the pandemic. This infectious lineage has resulted in the generation of sub-lineages such as B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.617.3.

Within these variants, the Delta variant has been found to be the most dominant as well as being 60% more transmissible than the Alpha (B.111.7) variant. It has been characterized as a variant of concern by the World Health Organisation (WHO).

This variant of SARS-CoV-2 has affected 92 countries, with the Indian population suffering the most, resulting in the second wave of the Coronavirus 2019 (COVID-19) pandemic that has affected millions of Indian citizens.

Delta variants have been reported to show lower antibody neutralization to several vaccines developed for the original SARS-CoV-2 outbreak. Consequently, some individuals continued to be infected by the Delta variant of the virus after receiving their vaccinations.

The Indian Council of Medical Research has undertaken a study to understand the protective immune response to infection with Delta variants and the effects of vaccines on this response in light of the limited amount of research available.

The researchers aimed to evaluate the vaccine-induced humoral immune response in individuals who had received the Covishield vaccine, investigating: 1) those receiving one dose, 2) receiving two doses, 3) COVID-19 convalescents with one dose of the vaccine, 4) COVID-19 convalescents with two doses of the vaccine as well as 5) breakthrough COVID-19 cases.

A pre-print version of the paper is available on the bioRxiv* server, while the article undergoes peer review.

Study: Neutralization of Delta variant with sera of Covishield vaccinees and COVID-19 recovered vaccinated individuals. Image Credit: NIAID

Covishield

Covidshield ChAdOx1 nCoV-19 is a vaccine that has been rolled out as part of the national COVID-19 vaccination program in India since 16 January 2021. The vaccine is a replication-deficient viral vector based-SARS-CoV-2 recombinant. A study in England and Wales has shown to have significant immune responses after the first dose and complete seroconversion after the second dose. However, because the Delta variant is mutated in the spike region, this could pose a real challenge to vaccines targeting the spike gene.

Neutralizing antibody levels

The research team had previously assessed and concluded that a reduction in the neutralizing antibody titer in the serum samples had been found in those vaccinated with Covishield against the Kappa variant.

When investigating the neutralizing antibody levels in the vaccinated individuals against the Delta variant, the researchers found that there had also been a reduction in the serum of participants. This further supported the hypothesis that there is still susceptibility to being infected by the Delta variant of the virus with individuals who had received two doses of the vaccine.

However, investigations of convalescent patients who had recovered from COVID-19 and had received either one or two doses of the vaccine had illustrated higher neutralizing antibody titers compared to those who were given the vaccine but did not suffer from the SARS-CoV-2 infection.

This led to the conclusion that even one dose of the vaccine for these convalescent participants was enough to provide sufficient protection both against re-infection as well as against any emerging novel variants.

This finding supports the role of cross-reactive SARS-CoV-2-specific T cell-mediated immune response, with similar findings from different studies also demonstrating that single-dose vaccinations after recovery from a previous infection can be effective against re-infection.

When analyzing the IgG immunoglobulin levels specific to the SARS-CoV-2 RBD (receptor-binding domain) in the various participant categories, the team had observed that IgG specific to RBD protein had a higher antibody response in the convalescent patients and breakthrough cases. This further suggests the higher level of protection that can be found in these participants compared to those without infection who had been administered with the vaccine.

The study mentions that the priming of the immune system memory is either established through natural infection or vaccination. However, while spike-specific IgG antibodies and virus-specific memory T cells can decrease over time, the population of virus-specific memory B cells may increase. This would explain the higher levels of protection that convalescent patients with one dose of the vaccine may experience as their immune system may be more prepared for re-infection, enabling them to better combat this as well as novel strains.

The long-term follow-up of participants could provide insight into the impact of vaccination and natural infection on the long-term effectiveness of Covishield's protection against SARS-CoV-2. Tracking breakthrough infections is crucial for spotting unexpected changes. Among the study's shortcomings is the lack of information on cellular responses that may be relevant to cross-reactive protection. Following the third dose of Covidshield ChAdOx1 nCoV-19, the antibody titers and spike-specific T-cell responses had increased significantly above those after the second dose.

The paper concludes, "The monitoring of breakthrough infections would allow us to discern how new variants or VOCs affect the escape of vaccination-induced immunity. The data has repeatedly demonstrated that if the individuals are infected post-vaccination, they are protected from severe disease."

*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

Marzia Khan

Marzia Khan is a lover of scientific research and innovation. She immerses herself in literature and novel therapeutics which she does through her position on the Royal Free Ethical Review Board. Marzia has a MSc in Nanotechnology and Regenerative Medicine as well as a BSc in Biomedical Sciences. She is currently working in the NHS and is engaging in a scientific innovation program.