Reduced humoral response 3 months following BNT162b2 vaccination in SARS-CoV-2 uninfected residents of long-term care facilities

  1. Macedonia Trigueros
  2. Edwards Pradenas
  3. Dolors Palacín
  4. Francisco Muñoz-López
  5. Carlos Ávila-Nieto
  6. Benjamin Trinité
  7. Josep Maria Bonet-Simó
  8. Mar Isnard
  9. Nemesio Moreno
  10. Silvia Marfil
  11. Carla Rovirosa
  12. Teresa Puig
  13. Eulàlia Grau
  14. Anna Chamorro
  15. Ana Martinez
  16. Ruth Toledo
  17. Marta Font
  18. Jordi Ara
  19. Jorge Carrillo
  20. Lourdes Mateu
  21. Julià Blanco
  22. Bonaventura Clotet
  23. Nuria Prat
  24. Marta Massanella
  25. on behalf of the CoronAVI@S and the KING cohort extension studies
  26. S Reyes Carrión
  27. N Salarich Solà
  28. A Vidal
  29. R Alvarez Viñallonga
  30. J Tornero
  31. E Vilamala
  32. C Suarez
  33. T Gonzalo
  34. L Perez
  35. D Sans
  36. A Blancas Loras
  37. A Garcia Archer
  38. J Borràs
  39. S Cervelló
  40. G Llados
  41. S España
  42. J R Santos
  43. C Loste
  44. C López
  45. I Casafont
  46. C Estany
  47. C Rodriguez
  48. J Moreno-Muñoz
  49. A Prats
  50. C Herrero
  51. A Garcia
  52. M Montero
  53. P Tornero
  54. N Gonzalez Palomares
  55. A Grajea
  56. L Ortiz
  57. C Miranda
  58. E Abad
  59. D Figueroa
  60. A Mancera
  61. S Gonzalez Alonso
  62. M Perez
  63. L Esteban
  64. M Ortiz
  65. L Valls
  66. L Ceron
  67. T Baena
  68. C Puig
  69. M Cucurell
  70. J Puig

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Abstract

Background

SARS-CoV-2 vaccination is the most effective strategy to protect older residents of long-term care facilities (LTCF) against severe COVID-19, but primary vaccine responses are less effective in older adults. Here, we characterised the humoral responses of institutionalised seniors 3 months after they had received the mRNA/BNT162b2 vaccine.

Methods

plasma levels of SARS-CoV-2-specific total IgG, IgM and IgA antibodies were measured before and 3 months after vaccination in older residents of LTCF. Neutralisation capacity was assessed in a pseudovirus neutralisation assay against the original WH1 and later B.1.617.2/Delta variants. A group of younger adults was used as a reference group.

Results

three months after vaccination, uninfected older adults presented reduced SARS-CoV-2-specific IgG levels and a significantly lower neutralisation capacity against the WH1 and Delta variants compared with vaccinated uninfected younger individuals. In contrast, COVID-19-recovered older adults showed significantly higher SARS-CoV-2-specific IgG levels after vaccination than their younger counterparts, whereas showing similar neutralisation activity against the WH1 virus and an increased neutralisation capacity against the Delta variant. Although, similarly to younger individuals, previously infected older adults elicit potent cross-reactive immune responses, higher quantities of SARS-CoV-2-specific IgG antibodies are required to reach the same neutralisation levels.

Conclusions

although hybrid immunity seems to be active in previously infected older adults 3 months after mRNA/BNT162b2 vaccination, humoral immune responses are diminished in COVID-19 uninfected but vaccinated older residents of LTCF. These results suggest that a vaccine booster dose should be prioritised for this particularly vulnerable population.

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  1. Version published to 10.1093/ageing/afac101
  2. ScreenIT

    SciScore for 10.1101/2021.11.18.21266502: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The CoronAVI@S study and the KING cohort extension were approved by the Ethics Committee Boards from the Institut Universitari d’Investigació en
    Consent: All participants provided written informed consent before inclusion.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Determination of anti-SARS-CoV-2 antibodies: The presence of anti-SARS-CoV-2 antibodies against S2+RBD or NP in plasma samples was evaluated using an in-house developed sandwich-ELISA, as previously described [15].
    anti-SARS-CoV-2
    suggested: None
    S2+RBD
    suggested: None
    Software and Algorithms
    SentencesResources
    The CoronAVI@S study and the KING cohort extension were approved by the Ethics Committee Boards from the Institut Universitari d’Investigació en
    KING
    suggested: (KING, RRID:SCR_009251)
    Standard curve was calculated by plotting and fitting the log of standard dilution (in arbitrary units) vs. response to a 4-parameter equation in Prism 8.4.3 (GraphPad Software).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    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:
    Even though an assessment of the immune response several months after vaccination has been performed, our study has some limitations. First, the relatively small number of participants, especially for the uninfected elder group, which was unexpectedly low. While 64% of the cohort tested positive by PCR in massive tests screenings during outbreaks, SARS-CoV-2 serologic test revealed that 84% of residents suffered from COVID-19. In addition, we did not assess specific SARS-CoV-2 cellular responses before and after vaccination, which could also be used as a correlate of protection [28]. Further follow-up of the immune responses, as well as registration of breakthrough infections in COVID-19-uninfected residents from LTCF will allow to define the immune correlate of protection in this frail and vulnerable population. To this purpose, determination of the quality of humoral immune response, using functional neutralization assays, is necessary in the population older than 65 years. Taken together, our results suggest that only the uninfected-residents, who do not develop adequate immune responses, will clearly benefit from a booster vaccine dose; an adapted vaccination calendar would be necessary to respond to the immune needs of this vulnerable population. Importantly, hybrid immunity seems to be active in elders and can be relevant to design vaccine boosting campaigns.

    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.

  3. Version published to 10.1101/2021.11.18.21266502v1 on medRxiv