Home Immunity The strength and extent of antibody responses elicited by hybrid immunity to vaccination or COVID-19 infection alone

The strength and extent of antibody responses elicited by hybrid immunity to vaccination or COVID-19 infection alone


In a recent study published on medRxiv* preprint server, researchers assessed neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after receiving a dose of vaccine.

Study: Strong neutralizing antibody responses to SARS-CoV-2 variants after a single vaccine dose in subjects previously infected with SARS-CoV-2. Image Credit: CI Photos/Shutterstock


Evidence shows that a history of SARS-CoV-2 infection stimulates the immune system, causing hybrid immunity in individuals recovered from coronavirus disease 2019 (COVID-19) after subsequent vaccination. However, further research is essential to understand the extent and efficacy of hybrid immunity stimulated by severe or mild COVID-19 infection.

About the study

In the current study, researchers compared the strength and robustness of antibody responses obtained in vaccinated individuals with a history of COVID-19 infection and in uninfected individuals.

The team obtained blood samples from individuals recovered after administering a dose of the COVID-19 vaccine. COVID-19 severity was defined as mild or severe, with mild infection including laboratory-confirmed SARS-CoV-2 infection without reported hospitalization, and severe infection including cases of SARS-CoV-2 infection. Laboratory-confirmed CoV-2 requiring hospital treatment. Data related to patient demographics, COVID-19 vaccination history, and clinical characteristics were collected from the National Immunization Registry and the National Infectious Disease Registry.

The team detected 2,586 subjects aged 18 and over who tested positive for the polymerase chain reaction (PCR) for COVID-19 between February and April 2020. Blood samples were taken from 1,074 patients to determine the concentration of SARS-CoV-2 specific serum antibodies at eight and 13 months after diagnosis of COVID-19. The study included patients who received one dose of BNT162b2 or ChAdOx1 COVID-19 vaccines seven to 90 days or two doses of BNT162b2 seven to 120 days prior to the 13-month sampling.

The team randomly selected matched serological samples from 30 of 55 study participants with a history of COVID-19 infection with subsequent vaccination with BNT162b2 22–90 days prior to sample collection for titer determination. of neutralizing antibodies (NAb) against SARS-CoV-2 strain wild type (WT) and variants Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron ( B.1.1.529/BA.1) . Samples were collected from 15 participants 59 to 90 days after vaccination. Of the 15 people, eight had a history of severe COVID-19. Another 15 participants were selected to collect blood samples 21-30 days after COVID-19 vaccination by matching the severity of disease, sex and age of the participant to the first group.

Serum samples were collected from 640 participants aged 18 years and older nearly 13 months after PCR-confirmed diagnosis of SARS-CoV-2 WT infection without any history of COVID-19 vaccination. The team also obtained serum samples from a total of 38 participants with previous SARS-CoV-2 WT infection but no history of COVID-19 vaccination at an average of 51 days and 118 days post-treatment. infection.


Study results showed that 97% and 89% of participants tested positive for the presence of SARS-CoV-2 spike (S) immunoglobulin G (IgG) and NAbs against SARS-CoV-2 strain. CoV-2 WT before receiving the COVID-19 vaccination eight months after diagnosis of COVID-19. The team also noted that a single dose of the COVID-19 vaccine caused nearly 20 times higher IgG levels in people with a history of COVID-19 infection compared to uninfected people. Additionally, hybrid immunity stimulated following mild infection resulted in significantly higher mean S-IgG levels compared to concentrations seen in individuals experiencing only mild infection.

The team also noted a twice higher concentration of S-IgG following a diagnosis of infection after vaccination with a dose of BNT162b2 compared to a double vaccination with BNT162b2 alone. Nearly 98% of patients with hybrid immunity and 100% of doubly vaccinated patients showed NAbs against SARS-CoV-2 WT. A comparison of the neutralization capacity of Abs that target the viral spike protein showed that an almost three-fold higher neutralization capacity of Abs was achieved through hybrid immunity as opposed to that after double vaccination. Additionally, while mean antibody levels declined 90 days after hybrid immunity was achieved, 97% of individuals had detectable levels of NAbs.

A vaccine dose of BNT162b2 elicited substantially elevated IgG and NAb titers in subjects with a history of COVID-19 infection compared to induction observed prior to vaccination. The team also found the highest average NAbs titers against the WT strain, but reduced titer levels against the Alpha, Beta, Delta, and Omicron BA.1 variants. Variations in mean NAb titer levels ranged from 30 to 46 and eight to 27 depending on the infecting strain for the severe and mild disease cohorts, respectively. This indicated that hybrid immunity was more pronounced after severe infection than after mild infection.


Overall, study results showed that one dose of COVID-19 vaccine given nine to 12 months after diagnosis of COVID-19 significantly increased anti-nab antibody and IgG levels. specific to spikes in people with a history of SARS-CoV-2 WT infection.

*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.