Does the duration between SARS-CoV-2 infection and vaccination affect immunity?

In a recent study published on medRxiv*preprint server, researchers at Oregon Health & Science University assessed the impact of time between coronavirus disease 2019 (COVID-19) infection and vaccination on immunity to infection.

As the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections continues, long-term immunity against COVID-19 has become more critical. Global public health concerns have been heightened by the continued emergence of new variants of SARS-CoV-2 with higher transmissibility and infectivity than previous variants. Further investigation is needed to understand various aspects of SARS-CoV-2 immunity, such as the temporal profile, especially between infection and repeat vaccination.

To study: Time between vaccination and infection impacts immunity against SARS-CoV-2 variants. Image Credit: Ja_inter / Shutterstock

About the study

In the present study, researchers assessed the effect of combined COVID-19 infection and vaccination or hybrid immunity and its associated timing on the quantity and quality of antibodies obtained.

The team recruited ten people from December 2020 to March 2021 who tested positive for COVID-19 by polymerase chain reaction (PCR) before being vaccinated. Blood samples were taken before and after a two-dose BNT162b2 vaccination. Additionally, 20 sex- and age-matched individuals with no self-reported history of prior COVID-19 infection were recruited and their blood samples collected before and after vaccination. In addition, serum neutralizing titers were estimated and compared for these two cohorts via a live virus focus reduction neutralization test (FRNT).

An additional cohort was recruited comprising 23 vaccinated individuals who did or did not exhibit hybrid immunity due to prior COVID-19 infection, as well as 23 subjects with vaccine breakthrough infections. Serological samples were obtained within 60 days of vaccination or breakthrough infection confirmed by PCR. Additionally, the team estimated spike-specific antibody levels for this cohort via enzyme immunoassay (ELISA).

The hybrid immune group included subjects diagnosed with SARS-CoV-2 infection nearly 40–404 days after vaccination and subjects vaccinated 35–283 days after COVID-19 diagnosis. The team characterized the association between neutralizing titers and antibody levels using age, sex, exposure interval and the time that elapsed between the last exposure and sample collection. samples. The cohort was further subdivided into 100-day exposure intervals.

Results

Study results revealed that serum neutralization titers increased for previously infected cohorts as well as naïve cohorts before and after COVID-19 vaccination. Titers were also significantly higher in people with a history of infection compared to those vaccinated against all strains, such as the original SARS-CoV-2 (WA1) and variants such as alpha, beta, and gamma variants. of concern (VOC). This indicated that hybrid immunity resulting from both natural infection and vaccination could lead to high titers of serum neutralizing antibodies.

ELISA performed on the largest cohort showed that the total antigen-proportions of specific antibodies 3.6 times higher due to hybrid immunity than after vaccination alone. Class-specific ELISA revealed that this phenomenon was due to the 3.7-fold increase in immunoglobulin (Ig)-G levels and a 3.2-fold increase in IgA levels. IgM levels showed no such variation between the two groups. Total antibody levels also increased 3.1-fold with hybrid immunity against SARS-CoV-2 spike protein(s).

The team also noted that neutralizing antibody titers against SARS-CoV-2 and all variants tested increased in the group with hybrid immunity compared to the vaccinated-only cohort. Neutralizing titers increased 8.4 times, 12.5 times, 22.7 times, 9.6 times, 19 times and 13.3 times against WA1, Alpha, Beta, Delta, Omicron BA.1 and Omicron BA. 2, respectively. The greatest increase was noted against the Beta and Omicron BA.1 and BA.2 subvariants.

In the hybrid immune group, neutralizing antibody titers and antibody levels were notably associated with the exposure interval. The most significant correlations were observed for SARS-CoV-2 spike-specific antibody levels and neutralization of WA1, Alpha, Delta, Beta, and Omicron BA.1 and BA.2. Additionally, the extent of elevation noted by the team varied between the different variants. By day 400, neutralizing titles increased 5.3x against WA1, 4.8x against Alpha, 11.5x against Beta, 11.2x against Delta, 17.6x against Omicron BA.1 and 14, 3 times against Omicron BA. 2. Between the 35-100 and 300-404 day exposure interval cohorts, neutralizing titers increased against WA1 by 4.2 times, Alpha by 4.1 times, Beta by 9.6 times, Delta by 7.1 times, Omicron BA.1 by 12.5 – times, and Omicron BA.2 by 10.7 times.

Conclusion

Study results showed that individuals with hybrid immunity exhibited robust SARS-CoV-2 neutralizing antibody responses against all variants, including the SARS-CoV-2 Omicron BA.2 subline. The team also found remarkably improved neutralizing titers when vaccination-infection time intervals were longer up to 400 days. These results suggest that anti-SARS-CoV-2 antibody responses undergo continuous maturation after primary exposure to the virus via infection or vaccination for at least 400 days since the last antigen exposure. The researchers believe these findings could extend to COVID-19 booster doses, which could result in higher protection against infection when given after longer intervals.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.