In a recent study published on the preprint server medRxiv*, researchers at Oregon Health & Science University assessed the impact of the duration between infection with coronavirus disease 2019 (COVID-19) and vaccination on the immunity against 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 exacerbated by the continuous emergence of new SARS-CoV-2 variants with higher transmissibility and infectivity than previous variants. Extensive research is needed to understand various aspects of SARS-CoV-2 immunity, such as the temporal profile, especially between infection and repeated vaccination.
Study: Time between vaccination and infection affects immunity against SARS-CoV-2 variants. Image credit: Ja_inter / Shutterstock
About the study
In the present study, the researchers evaluated the effect of combined COVID-19 infection and vaccination or hybrid immunity and its associated timing on the quantity and quality of antibodies elicited.
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 collected before and after a two-dose BNT162b2 vaccination. In addition, 20 sex- and age-matched individuals with no self-reported history of previous COVID-19 infection were recruited and blood samples were collected before and after vaccination. In addition, serum neutralization titers for these two cohorts were estimated and compared using a live virus focus reduction neutralization test (FRNT).
An additional cohort consisting of 23 vaccinated individuals who did and did not exhibit hybrid immunity due to prior COVID-19 infection was recruited along with 23 subjects with vaccine-innovative infections. Serological samples were obtained less than 60 days after vaccination or PCR-confirmed advanced infection. In addition, the team estimated spike-specific antibody levels for this cohort using an enzyme-linked immunosorbent assay (ELISA).
The hybrid immune group included subjects diagnosed with SARS-CoV-2 infection nearly 40 to 404 days after vaccination and subjects vaccinated between 35 and 283 days after diagnosis of COVID-19. The team characterized the association between neutralizing titers and antibody levels using age, gender, exposure interval, and time elapsed between last exposure and sample collection. The cohort was further subdivided into 100-day exposure interval bins.
results
The study results found that serum neutralization titers increased for the previously infected cohorts and for the naïve cohorts before and after vaccination against COVID-19. Titers were also markedly higher among individuals with a history of previous infection compared to those vaccinated against all strains, including the original SARS-CoV-2 (WA1) and variants such as the Alpha, Beta, and Gamma (VOC). This indicated that hybrid immunity resulting from both natural infection and vaccination could lead to high titers of neutralizing serum antibodies.
ELISA performed in the larger cohort showed that total antigen-specific antibody ratios were 3.6-fold higher due to hybrid immunity than after vaccination alone. Class-specific ELISA revealed that this phenomenon was due to a 3.7-fold increase in immunoglobulin (Ig)-G levels and a 3.2-fold increase in IgA levels. IgM levels did not show this variation between the two groups. Total antibody levels also increased 3.1-fold with hybrid immunity against the SARS-CoV-2 spike protein.
The team also noted that titers of neutralizing antibodies against SARS-CoV-2 and all variants tested were increased in the group with hybrid immunity compared to the cohort that was only vaccinated. Neutralizing titers increased 8.4-fold, 12.5-fold, 22.7-fold, 9.6-fold, 19-fold and 13.3-fold against WA1, Alpha, Beta, Delta, Omicron BA.1 and Omicron BA. 2, respectively. The highest increase was observed with the Beta and Omicron BA.1 and BA.2 subvariants.
In the hybrid immune group, neutralizing antibody titers and antibody levels were significantly associated with 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. In addition, the extent of elevation observed by the team varied between the different variants. At day 400, neutralizing titers increased 5.3-fold against WA1, 4.8-fold against Alpha, 11.5-fold against Beta, 11.2-fold against Delta, 17.6-fold against Omicron BA.1, and 14.3 times against Omicron BA. 2. Among the 35- to 100- and 300- to 404-day exposure interval cohorts, neutralizing titers increased by 4.2-fold against WA1, Alpha by 4.1-fold, Beta by 9.6-fold, Delta in 7.1 times, Omicron BA.1 in 12.5 times. -fold, and Omicron BA.2 by 10.7 times.
conclusion
The study findings showed that individuals with hybrid immunity displayed robust SARS-CoV-2 neutralizing antibody responses against all variants, including the SARS-CoV-2 Omicron BA.2 sublineage. The team also found significantly improved neutralizing titers when the vaccination-infection time intervals were longer up to 400 days. These findings suggested that anti-SARS-CoV-2 antibody responses undergo continuous maturation after primary exposure to the virus through infection or vaccination for at least 400 days from the last antigen exposure. The researchers believe these findings may extend to doses of the COVID-19 booster vaccine, which could gain greater protection against infection when given after longer intervals.
*Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.
Journal reference:
- Time Between Vaccination and Infection Affects Immunity to SARS-CoV-2 Variants Timothy A. Bates, Hans C. Leier, Savannah K. McBride, Devin Schoen, Zoe L. Lyski, David X. Lee, William B. Messer, Marcel E. Curlin, Fikadu G. Tafesse, medRxiv 2023.01.02.23284120, DOI: