The delta variant of SARS-CoV-2, the virus that causes COVID-19, is one of multiple variants to exhibit increased resistance to antibodies as well as higher transmissibility. It is unclear if vaccination or prior infection with the original Wuhan Hu-1 strain is effective against these emerging variants. But now, a new report suggests individuals who have recovered from infection with the original SARS-CoV-2 strain are protected from variants such as delta, especially following vaccination.

A virus strain is considered the “parent” form of a virus. For example, SARS-CoV-1 and SARS-CoV-2 are strains of the broader SARS-CoV line of viruses. To be considered a variant, a virus must have sufficient mutations to change a portion of its genetic code. In the case of the delta variant, increased transmissibility is the result of genetic changes to the receptor binding domain, a portion of the viral spike protein. This protein enables viruses to enter cells and is the main target of SARS-CoV-2 vaccines. Its genetic change in the delta variant has scientists concerned that individuals who have recovered from the original virus or an early variant may not be protected against later variants with altered spike proteins.

During infection with a virus, the innate immune system immediately produces inflammation to fight the infection. Within days or weeks, the adaptive immune system produces antibodies that are specific to the virus. These antibodies bind to a small piece of the viral particle, called an antigen. Plasma B cells are the white blood cells responsible for producing antibodies; however, these cells steadily decrease in number over time and do not protect against reinfection with the same virus. Memory B cells store the genetic information needed to produce virus-specific antibodies upon reinfection.

The authors of the novel report recruited 63 participants between the ages of 26 and 73 years old who were convalescent, meaning they had recovered from SARS-CoV-2 infection. Some participants had received a vaccine (only mRNA vaccines were included) and others had not. The researchers collected blood samples from their participants at about six weeks, six months, and one year following infection in order to characterize their immune responses specifically to the receptor binding domain of the SARS-CoV-2 spike protein. Immunity measures included specificity (the number of antigens to which an antibody will bind), reactivity (the strength to which an antibody binds its antigen), and neutralizing activity (the antibodies' ability to block infection).

Their analysis revealed that convalescent participants who had not been vaccinated maintained their plasma antibody levels 12 months following infection, providing protection from reinfection. Notably, convalescent participants who had received an mRNA vaccine had 30 times more antibodies and 50 times greater neutralizing activity against the original SARS-CoV-2 strain 12 months following infection than unvaccinated convalescent participants. Neutralizing activity against the alpha, beta, iota, and gamma variants was also ten times greater at 12 months compared to vaccinated individuals who have never had the virus. This means the immune system will react strongly if a vaccinated convalescent individual catches one of the viral variants.

Antibody-producing B cells evolved over time in both vaccinated and unvaccinated convalescent participants; however, receiving an mRNA vaccine increased receptor binding domain antibodies eightfold. Without vaccination, convalescent participants lost a significant portion of antibodies that were specific for the receptor binding domain of the spike protein at six months post-infection, putting them at greater risk for reinfection. The authors showed that memory B cells continually mutate their antibody structures to increase reactivity and specificity over time, providing stronger immunity against a wider array of strains.

The authors concluded that immunity in convalescent individuals is long lasting. Vaccination provides additional protection against SARS-CoV-2 variants in convalescent individuals. However, an article covered in this edition of the Science Digest suggests current mRNA vaccines may be less effective against the delta variant in vaccinated people who have never had a SARS-CoV-2 infection.

• Link to full report.