When it comes to vaccination, patients who were previously infected with COVID-19 are in a different situation than those who weren't—at least initially.

That's according to a new study accepted for publication in Nature Research. Yale University School of Medicine researchers also determined that the two mRNA vaccines provide protection against multiple variants of the SARS-CoV-2 virus, including the highly infectious Delta variant.

Patients previously infected exhibited a more robust immune response to all variants than those who were uninfected and fully vaccinated, according to the study. The authors point out, "The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination."

The study team focused on the development of anti-SARS-CoV-2 antibody and T-cell responses in recovered or na•ve (uninfected) recipients of mRNA vaccines to protect against SARS-CoV-2.

The researchers note, "While previously infected individuals sustained higher antibody titers than uninfected individuals post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain after the second vaccine dose. T-cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination."

The authors add that their comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants demonstrated a range of reduction in the neutralization capacity associated with specific mutations in the spike gene. Of those, lineages with E484K and N501Y/T (e.g., B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (e.g., B.1.617.2).

"While both groups retained neutralization capacity against all variants, plasma from previously infected vaccinated individuals displayed overall better neutralization capacity when compared to plasma from uninfected individuals that also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the impact of emerging variants on antibody neutralizing activity," the researchers advise."Vaccines induce high levels of antibodies against Delta and most variants," added co-corresponding author Akiko Iwasaki, PhD, the Waldemar Von Zedtwitz professor of immunobiology. "And two shots are better than one."

The study involved 40 healthcare workers at the Yale-New Haven Hospital who were enrolled between November 2020 and January 2021, with a total of 198 samples. All received either Pfizer-BioNTech or Moderna mRNA vaccines.  

"We found that mRNA vaccines induced high titers of virus-specific antibodies that declined over time, as previously reported," the authors explain. "After the first vaccine dose, over 97% vaccinated participants developed virus-specific IgG titers, which increased to 100% after the second dose. IgG titers against the S protein, spike subunit 1 (S1), and receptor-binding domain (RBD) peaked 7 days post-second vaccination dose."

They add that no differences were observed in antibody levels between vaccinated participants of different sexes and after stratification by age, adding, "Consistent with previous reports, we found that virus-specific IgG levels were significantly higher in the previously infected vaccinated group than the uninfected vaccinated group. As expected, given the absence of sequences encoding nucleocapsid (N) antigens in the mRNA vaccines, anti-N antibody titers remain stable over time for previously infected vaccinated individuals, and were not affected by vaccination in both the uninfected and previously infected groups."

The authors conclude, "Our data indicate that despite faster and more exuberant antibody responses to viral proteins by previously infected vaccinated than uninfected vaccinated individuals, vaccination led to overall similar levels of neutralizing antibodies (NAb) after the second dose. Recovering from an initial infection is like getting a first vaccine shot," Iwasaki explained, suggesting that a booster shot could have a similar effect, increasing the presence of antibodies and T cells that protect against infections.

Nathan Grubaugh, PhD, associate professor of epidemiology at Yale, adds that the study provided some insight into breakthrough infections among the vaccinated with COVID-19. "The Delta variant is more infectious than earlier variants," he advised. "The high transmissibility of the variant, not its escape from our vaccine-induced immune response, best explains infections among the vaccinated."

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

« Click here to return to COVID-19 update.