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

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


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

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


Evidence shows that a history of SARS-CoV-2 infection stimulates the immune system, eliciting 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 present study, researchers compared the strength and robustness of antibody responses elicited in vaccinated individuals having a history of COVID-19 infection and uninfected persons.

The team obtained blood samples from recovered individuals after administering one dose of the COVID-19 vaccine. COVID-19 severity was defined as either mild or severe, wherein mild infection comprised laboratory-confirmed SARS-CoV-2 infection with no reported hospitalization, and severe infection included laboratory-confirmed SARS-CoV-2 infection cases that required hospital treatment. Data related to patient demographics, COVID-19 vaccination history, and clinical characteristics were collected from the National Vaccination Register and the National Infectious Disease Register.

The team detected 2,586 subjects aged 18 years and above who tested polymerase chain reaction (PCR) positive for COVID-19 between February and April 2020. Blood samples were collected from 1074 patients to determine the concentration of SARS-CoV-2 specific serum antibodies at eight and 13 months after COVID-19 diagnosis. The study included patients administered one dose of either BNT162b2 or ChAdOx1 COVID-19 vaccines seven to 90 days or two doses of BNT162b2 seven to 120 days before the 13-month sampling.

The team randomly selected paired serological samples from 30 out of the 55 study participants having a history of COVID-19 infection with subsequent vaccination with BNT162b2 22 to 90 days before the collection of samples for determination of neutralizing antibodies (NAb) titers against the SARS-CoV-2 wild-type (WT) strain and the Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529/BA.1) variants. Samples were obtained from 15 participants 59 to 90 days post-vaccination. Among the 15 individuals, eight had a history of severe COVID-19. Another 15 participants were selected to collect blood samples 21 to 30 days after the COVID-19 vaccination by matching the participant’s disease severity, gender, and age to the first group.

Serum samples were collected from 640 participants aged 18 years and above almost 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 having a previous SARS-CoV-2 WT infection but no history of COVID-19 vaccination at an average of 51 days and 118 days after infection.        


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

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

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


Overall, the study findings showed that one COVID-19 vaccine dose administered nine to 12 months after COVID-19 diagnosis significantly increased the NAb and spike-specific IgG levels in individuals having 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 regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Ekstrom, N. et al. (2022) "Strong neutralizing antibody responses to SARS-CoV-2 variants following a single vaccine dose in subjects with previous SARS-CoV-2 infection". medRxivdoi:

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Antibodies, Antibody, Blood, Coronavirus, Coronavirus Disease COVID-19, covid-19, Efficacy, Hospital, Immune System, immunity, Immunoglobulin, Laboratory, Omicron, Polymerase, Polymerase Chain Reaction, Protein, Research, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Spike Protein, Syndrome, Vaccine

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Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.

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