Hybrid immunity in older adults is associated with reduced SARS-CoV-2 infections following BNT162b2 COVID-19 immunisation

Scott J C Pallett; Joseph Heskin; Fergus Keating; Andrea Mazzella; Hannah Taylor; Aatish Patel; Georgia Lamb; Deborah Sturdy; Natalie Eisler; Sarah Denny; Esmita Charani; Paul Randell; Nabeela Mughal; Eleanor Parker; Carolina Rosadas de Oliveira; Michael Rayment; Rachael Jones; Richard Tedder; Myra McClure; Elisabetta Groppelli; Gary W Davies; Matthew K O'Shea; Luke S P Moore

doi:10.1038/s43856-023-00303-y

Hybrid immunity in older adults is associated with reduced SARS-CoV-2 infections following BNT162b2 COVID-19 immunisation

Commun Med (Lond). 2023 Jun 16;3(1):83. doi: 10.1038/s43856-023-00303-y.

Authors

Scott J C Pallett^#^{1

2}, Joseph Heskin^#¹, Fergus Keating³, Andrea Mazzella⁴, Hannah Taylor⁵, Aatish Patel¹, Georgia Lamb¹, Deborah Sturdy^{3

6}, Natalie Eisler³, Sarah Denny¹, Esmita Charani¹, Paul Randell⁷, Nabeela Mughal^{1

7}, Eleanor Parker⁸, Carolina Rosadas de Oliveira⁸, Michael Rayment¹, Rachael Jones¹, Richard Tedder⁸, Myra McClure⁸, Elisabetta Groppelli⁴, Gary W Davies¹, Matthew K O'Shea^{2

9}, Luke S P Moore^{10

11

12}

Affiliations

¹ Clinical Infection Department, Chelsea and Westminster NHS Foundation Trust, London, UK.
² Centre of Defence Pathology, Royal Centre for Defence Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
³ Royal Hospital Chelsea, Royal Hospital Road, London, UK.
⁴ Institute for Infection and Immunity, St George's University of London, London, UK.
⁵ Army Health Branch, Army Headquarters, Andover, UK.
⁶ Chief Nurse, Adult Social Care, UK Department of Health and Social Care, London, UK.
⁷ North West London Pathology, London, UK.
⁸ Department of Infectious Disease, Faculty of Medicine, Imperial College London, London, UK.
⁹ Institute of Immunology and Immunotherapy, College of Medical & Dental Sciences, University of Birmingham, Birmingham, UK.
¹⁰ Clinical Infection Department, Chelsea and Westminster NHS Foundation Trust, London, UK. luke.moore@nhs.net.
¹¹ North West London Pathology, London, UK. luke.moore@nhs.net.
¹² Imperial College London, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, London, UK. luke.moore@nhs.net.

^# Contributed equally.

Abstract

Background: Older adults, particularly in long-term care facilities (LTCF), remain at considerable risk from SARS-CoV-2. Data on the protective effect and mechanisms of hybrid immunity are skewed towards young adults precluding targeted vaccination strategies.

Methods: A single-centre longitudinal seroprevalence vaccine response study was conducted with 280 LCTF participants (median 82 yrs, IQR 76-88 yrs; 95.4% male). Screening by SARS-CoV-2 polymerase chain reaction with weekly asymptomatic/symptomatic testing (March 2020-October 2021) and serology pre-/post-two-dose Pfizer-BioNTech BNT162b2 vaccination for (i) anti-nucleocapsid, (ii) quantified anti-receptor binding domain (RBD) antibodies at three time-intervals, (iii) pseudovirus neutralisation, and (iv) inhibition by anti-RBD competitive ELISA were conducted. Neutralisation activity: antibody titre relationship was assessed via beta linear-log regression and RBD antibody-binding inhibition: post-vaccine infection relationship by Wilcoxon rank sum test.

Results: Here we show neutralising antibody titres are 9.2-fold (95% CI 5.8-14.5) higher associated with hybrid immunity (p < 0.00001); +7.5-fold (95% CI 4.6-12.1) with asymptomatic infection; +20.3-fold, 95% (CI 9.7-42.5) with symptomatic infection. A strong association is observed between antibody titre: neutralising activity (p < 0.00001) and rising anti-RBD antibody titre: RBD antibody-binding inhibition (p < 0.001), although 18/169 (10.7%) participants with high anti-RBD titre (>100BAU/ml), show inhibition <75%. Higher RBD antibody-binding inhibition values are associated with hybrid immunity and reduced likelihood of infection (p = 0.003).

Conclusions: Hybrid immunity in older adults was associated with considerably higher antibody titres, neutralisation and inhibition capacity. Instances of high anti-RBD titre with lower inhibition suggests antibody quantity and quality as independent potential correlates of protection, highlighting added value of measuring inhibition over antibody titre alone to inform vaccine strategy.

Plain language summary

Older adults continue to be at risk of COVID-19, particularly in residential care home settings. We investigated the effect of infection and vaccination on antibody development and subsequent SARS-CoV-2 infection in older adults. Antibodies are proteins that the immune system produces on infection or vaccination that can help respond to subsequent infection with SARS-CoV-2. We found that older adults produce antibodies to SARS-CoV-2 after 2-doses of Pfizer BioNTech BNT162b2 vaccine. The strongest immune responses were seen among those older adults who also had prior history of infection. The results highlight the importance of both antibody quality and quantity when considering possible indicators of protection against COVID-19 and supports the need for a third, booster, vaccination in this age group..