SARS-COV-2 antibody responses to AZD1222 vaccination in West Africa

  1. Adam Abdullahi
  2. David Oladele
  3. Michael Owusu
  4. Steven A. Kemp
  5. James Ayorinde
  6. Abideen Salako
  7. Douglas Fink
  8. Fehintola Ige
  9. Isabella A. T. M. Ferreira
  10. Bo Meng
  11. Augustina Angelina Sylverken
  12. Chika Onwuamah
  13. Kwame Ofori Boadu
  14. Kazeem Osuolale
  15. James Opoku Frimpong
  16. Rufai Abubakar
  17. Azuka Okuruawe
  18. Haruna Wisso Abdullahi
  19. Gideon Liboro
  20. Lawrence Duah Agyemang
  21. Nana Kwame Ayisi-Boateng
  22. Oluwatosin Odubela
  23. Gregory Ohihoin
  24. Oliver Ezechi
  25. Japhet Senyo Kamasah
  26. Emmanuel Ameyaw
  27. Joshua Arthur
  28. Derrick Boakye Kyei
  29. Dorcas Ohui Owusu
  30. Olagoke Usman
  31. Sunday Mogaji
  32. Adedamola Dada
  33. George Agyei
  34. Soraya Ebrahimi
  35. Lourdes Ceron Gutierrez
  36. Sani H. Aliyu
  37. Rainer Doffinger
  38. Rosemary Audu
  39. Richard Adegbola
  40. Petra Mlcochova
  41. Richard Odame Phillips
  42. Babatunde Lawal Solako
  43. Ravindra K. Gupta

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Abstract

Real-world data on vaccine-elicited neutralising antibody responses for two-dose AZD1222 in African populations are limited. We assessed baseline SARS-CoV-2 seroprevalence and levels of protective neutralizing antibodies prior to vaccination rollout using binding antibodies analysis coupled with pseudotyped virus neutralisation assays in two cohorts from West Africa: Nigerian healthcare workers ( n  = 140) and a Ghanaian community cohort ( n  = 527) pre and post vaccination. We found 44 and 28% of pre-vaccination participants showed IgG anti-N positivity, increasing to 59 and 39% respectively with anti-receptor binding domain (RBD) IgG-specific antibodies. Previous IgG anti-N positivity significantly increased post two-dose neutralizing antibody titres in both populations. Serological evidence of breakthrough infection was observed in 8/49 (16%). Neutralising antibodies were observed to wane in both populations, especially in anti-N negative participants with an observed waning rate of 20% highlighting the need for a combination of additional markers to characterise previous infection. We conclude that AZD1222 is immunogenic in two independent West African cohorts with high background seroprevalence and incidence of breakthrough infection in 2021. Waning titres post second dose indicates the need for booster dosing after AZD1222 in the African setting despite hybrid immunity from previous infection.

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  1. Version published to 10.1038/s41467-022-33792-x
  2. Version published to 10.21203/rs.3.rs-1834968/v1 on Research Square
  3. Version published to 10.1101/2022.05.04.22274668v2 on medRxiv
  4. ScreenIT

    SciScore for 10.1101/2022.05.04.22274668: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Study population and sampling: Health care workers (HCWs) and Health workers (HWs) at the Nigerian Institute of Medical Research (NIMR) and Federal Medical Center, Ebute Metta, volunteering to be vaccinated with two doses of AZD1222 eight weeks apart were recruited to the study following signed informed consent.
    IRB: Statistical analysis was performed using GraphPad Prism version 9.0. Ethics: This study was approved by the Institutional Review Board of NIMR (IRB-21-040).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Laboratory methods and sample testing: Binding IgG antibodies (Abs) against SARS-COV-2 receptor-binding domain (RBD), trimeric spike protein (S) and nucleocapsid protein (N) were measured using the Luminex-based SARS-CoV-2-IgG assay (Luminex) by flow cytometry as previously detailed8,16.
    Binding IgG
    suggested: None
    Differences between neutralization antibody titres in IgG anti-N participants with ID50>20 were compared by Kruskal Wallis non-parametric test.
    anti-N
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    For plasma neutralising antibody measurement, SARS-CoV-2 lentiviral pseudovirus (PV) were prepared by transfecting 293T cells with Wuhan-614G wild type (WT), B.1.617.2 (Delta) and BA.1 (Omicron) plasmids in conjunction with p8.91 HIV-1 gag-pol expression vector 17.
    293T
    suggested: None
    Pseudovirus neutralization was performed on Hela-ACE2 cells using SARS-CoV-2 spike PV expressing luciferase.
    Hela-ACE2
    suggested: JCRB Cat# JCRB1845, RRID:CVCL_B3LW)
    Software and Algorithms
    SentencesResources
    Statistical analysis was performed using GraphPad Prism version 9.0. Ethics: This study was approved by the Institutional Review Board of NIMR (IRB-21-040).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    The limitations of the study include a modest sample size and follow up period, though we had nearly 50 participants with sequential follow up data and samples and 140 baseline samples for binding Ab studies. The underlying community population of Lagos was not sampled in a systematic way given vaccine delivery was first undertaken in individuals in the health sector; therefore the findings may not be fully generalisable to the whole country or region. In addition we did not measure non-neutralising antibody activities in vaccinees. Furthermore we were not able to identify the variants causing breakthrough infections, although neutralisation profiling was consistent with breakthrougxh infections largely driven by Delta. We conclude that AZD1222 is immunogenic in this real world west African cohort with significantly higher than previously expected background seroprevalence and incidence of breakthrough infection over a short time period. Prior infection and breakthrough infection induced higher anti-SARS-CoV-2 Ab responses at 3 months post vaccine against all widely circulating VOC. However, plasma neutralisation against Omicron BA.1 was low at three months regardless of prior exposure. Two dose AZD1222 has been showed to generate lower neutralisation titres and efficacy across different settings, in comparison to mRNA vaccines2,3,28. mRNA vaccine ‘booster’ third doses induce broader, potent responses against Omicron BA.13,29 and reduce mortality in the elderly30. Therefore, ...

    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.
    • No protocol registration statement was detected.

    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.

  5. Version published to 10.1101/2022.05.04.22274668v1 on medRxiv