Long-term Durable Humoral Immune Response to Heterologous Antigenic Exposure Post six months by Natural SARS-CoV-2 Infection and Vaccination

  1. Gaurav Batra
  2. Deepika Rathna Murugesan
  3. Souvick Chattopadhyay
  4. Farha Mehdi
  5. Ayushi
  6. Mudita Gosain
  7. Savita Singh
  8. Soon Jyoti Das
  9. Suprit Deshpande
  10. Jayanta Bhattacharya
  11. Anil K Pandey
  12. Sankalp Jha
  13. Shweta Goswami
  14. Asim Das
  15. Tanima Dwivedi
  16. Nandini Sharma
  17. Suresh Kumar
  18. Pragya Sharma
  19. Seema Kapoor
  20. Pallavi Kshetrapal
  21. Nitya Wadhwa
  22. Ramachandran Thiruvengadam
  23. Rakesh Kumar
  24. Ritu Gupta
  25. Pramod Kumar Garg
  26. Shinjini Bhatnagar
  27. DBT Consortium for COVID-19 Research

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Importance

Both vaccination and natural infection lead to immunity and may augment mutual immune response against SARS-CoV-2. There is a need for an evidence-driven booster vaccination policy depending on durability of immune response.

Objective

To determine the durability of humoral immune response with varying age, vaccine type, duration, and previous natural infection at least six months after complete vaccination with ChAdOx1 nCov-19 or BBV152.

Design

Cross-sectional observational study conducted between November 2021 and January 2022.

Setting

Participants were drawn from a DBT COVID-19 Research Consortium cohort in Delhi National Capital Region, India.

Participants

We included 2003 individuals who had completed six months after complete vaccination: (i) vaccination with ChAdOx1 nCoV-19 and aged 18-59 years, (ii) vaccination with ChAdOx1 nCoV-19 and aged ≥60 years (iii) vaccination with BBV152 and aged 18-59 years (iv) vaccination with BBV152 and aged ≥60 years (v) vaccination with either vaccine plus SARS-CoV-2 infection referred as those having hybrid immunity. A group of 94 unvaccinated individuals was also included for comparison.

Exposure

Age, vaccination type, prior SARS-CoV-2 infection and duration from vaccination/infection.

Main Outcome(s) and Measure(s)

Humoral immune response determined by anti-RBD IgG concentrations and the presence of anti-nucleocapsid IgG.

Results

The serum anti-RBD IgG antibodies were detected (cut-off 24 BAU/ml) in 85% participants with a median titer of 163 (IQR 73, 403) BAU/ml. In the hybrid immunity group, 97.6% [295 (IQR 128, 687) BAU/mL] tested positive for anti-RBD IgG compared to 81.3% [139 (IQR 62, 326) BAU/ml] of only vaccinated participants [χ2 test: p <0.001]. The median anti-RBD IgG titers were higher in the ChAdOx1 nCoV-19 versus BBV152 groups. The median anti-RBD IgG titer in the anti-nucleocapsid positive participants [326 (IQR 132, 739) BAU/ml] was significantly higher than in those without anti-nucleocapsid antibodies [131 (IQR 58, 288) BAU/ml; p <0.001]. The IgG anti-RBD antibodies was present in 85% of participants beyond a median of 8 months after complete vaccination.

Conclusions and Relevance

Considering the wide seropositivity rates due to natural SARS-CoV-2 infection, recommendation for boosters should take into account past infections in the population.

Key points

Question

What is the extent of waning of humoral immune response in various groups of vaccinated individuals at least six months after complete vaccination with ChAdOx1 nCov-19 or BBV152 with or without prior natural infection?

Findings

Cross-sectional observational study demonstrates persistence of anti-RBD IgG in 85% of participants even beyond a median of 8 months after complete vaccination. The antibody concentrations were significantly higher in those with hybrid immunity.

Meaning

Humoral immunity may last longer due to heterologous antigenic exposure following vaccination and natural infection emphasizing the need for contextualizing the booster policy.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2022.02.23.22271381: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: Written informed consent was obtained from the study participants.
    IRB: Institute ethics committees approved the study.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisWe estimated a sample size of at least 296 participants for each group to detect a decline of anti-IgG RBD by 30% after 6 months of vaccination with 80% power and at 5% significance after adjusting for multiple comparisons.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-RBD IgG concentrations in the plasma samples were determined by enzyme-linked immunosorbent assay (ELISA) as described earlier with minor modifications and are reported as BAU/mL.5 In addition, anti-nucleocapsid antibodies were detected using a qualitative ELISA.
    Anti-RBD IgG
    suggested: None
    anti-nucleocapsid
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has a few limitations, inability to unequivocally identify individuals with prior infection, and a small sample size of unvaccinated group, a reflection of >90% of eligible population having been vaccinated in India as in many other countries. Our data may guide policy for a booster dose. Considering the wide seropositivity rates due to natural infection, the priority for a booster should be for vulnerable and high-risk groups.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2022.02.23.22271381 on medRxiv