The coronavirus disease 2019 (COVID-19) pandemic caused worldwide health and economic crises. Many countries introduced lockdowns to help reduce the strain on health services. Recently with the help of mass vaccination schemes, drug repurposing programmes, and monoclonal antibodies, the pandemic has begun to be brought under control.

Study: mRNA vaccination of naive and COVID-19-recovered individuals elicits potent memory B cells that recognize SARS-CoV-2 variants. Image Credit: Kateryna Kon/ Shutterstock

However, worries are rising over variants of concern, such as the Delta variant, which is known to avoid both vaccine-induced and natural immunity. In a study published in Immunity, researchers have investigated the effect that memory B cells produced in individuals who have received an mRNA vaccine have against severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) variants.

Background

Traditionally, vaccines are manufactured from attenuated strains of the virus. The immune system is exposed to the attenuated form, allowing it to recognize viral cell surface proteins without risk of infection. However, in rare cases, the attenuated form can gain new traits from active viruses already inside the body, leading to safety concerns.

mRNA vaccines avoid this issue; they use the cells own machinery to transcribe an mRNA strand encoding a viral protein. Without any structural proteins or any way to reproduce viral DNA, these safety issues are circumvented.

Most current vaccines against SARS-CoV-2 target the receptor-binding domain (RBD) of the S1 subunit of the spike protein. The spike protein is essential for SARS-CoV-2 pathogenicity – the RBD is responsible for viral cell entry, and the N-terminal domain of the S2 subunit is required for membrane fusion.

Many variants of concern (VOCs) have mutations that alter the conformation of the spike protein, and studies have seen significantly lower antibody binding to altered spike proteins. Still, so far, the vaccines remain largely effective.

The study

The researchers examined two groups of vaccinated individuals, those who had been previously infected with the disease and those who had not. The individuals were further split into those who had suffered severe and mild COVID-19, with severe defined as requiring oxygen. A total of 17 severe cases and 26 mild cases were found.

All had received one dose of the Pfizer mRNA vaccine over six months after infection. For the virus-naïve individuals, they recruited 25 healthcare workers with no evidence of previous SARS-CoV-2 infection who had all received two doses of the vaccine. The study describes both of these cohorts as having received a 'boost', the second set from the second dose and the first set from prior COVID-19 infection.

When the pre-and post-boost IgG serum titres were measured in previously convalescent individuals, strong increases were seen following vaccination, with an average of a 24-fold increase in titre for severe patients and a 53-fold boost in mild patients. Naïve patients received an average 25-fold increase following their second dose.

The scientists also tested the ability of sera gathered from the individuals to neutralize SARS-CoV-2. They used a focus reduction assay against SARS-CoV-2 carrying the D614G mutation, which changes the spike protein structure. It is unusual to test against authentic SARS-CoV-2, and most researchers use pseudoviruses that require significantly fewer safety measures.

Sera gathered from previously convalescent individuals with both mild and severe COVID-19 showed strong neutralizing potency against the mutated virus. While the naïve individuals showed significantly lower activity, successful neutralization was seen.

Conclusion

The authors conclude that their research shows that both naïve and previously infected vaccinated individuals show a high-affinity response against the wild-type SARS-CoV-2 RBD and display significant neutralization activity and recognition of RBD variants.

Naïve individuals show much slower responses to RBD variants, but recent studies suggest that the affinity and diversity of this response will improve with time. These data could be critical for informing public health policymakers and healthcare workers at a time when VOCs remain the largest coronavirus-based threat, with the Delta variant accounting for the vast majority of new cases worldwide.

Knowing the threat posed to vaccinated individuals and how immunity is likely to change over time is essential for allocating second doses and even booster doses for at-risk groups such as the elderly, immunocompromised, or those with serious respiratory diseases.

Written by

Sam Hancock

Sam completed his MSci in Genetics at the University of Nottingham in 2019, fuelled initially by an interest in genetic ageing. As part of his degree, he also investigated the role of rnh genes in originless replication in archaea.