Evolution of long-term vaccine induced and hybrid immunity in healthcare workers after different COVID-19 vaccination regimens: a longitudinal observational cohort study

Abstract

Both infection and vaccination, alone or in combination, generate antibody and T cell responses against SARS–CoV–2. However, the maintenance of such responses – and hence protection from disease – requires careful characterisation. In a large prospective study of UK healthcare workers (PITCH, within the larger SIREN study) we previously observed that prior infection impacted strongly on subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. Here, we report longer follow up of 684 HCWs in this cohort over 6–9 months following two doses of BNT162b2 or AZ1222 (Oxford/AstraZeneca) vaccination and following a subsequent BNT162b2 booster vaccination. We make three important observations: Firstly, the dynamics of humoral and cellular responses differ; binding and neutralising antibodies declined whereas T and B cell responses were better maintained after the second vaccine dose. Secondly, vaccine boosting restored IgG levels to post second dose levels and broadened neutralising activity against variants of concern including omicron BA.1, alongside further boosting of T cell responses. Thirdly, prior infection maintained its impact driving larger T cell responses compared to never infected people, including after the third dose. In conclusion, the maintenance of T cell responses in time and against variants of concern may account for continued protection against severe disease.

Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses

“…No significant differences between previously-infected and naive participants were seen in spike- or nucleocapsid-specific secretory IgA (sIgA) from nasal lining fluid (Figure 1E & 1F), with equivalent human angiotensin-converting enzyme 2 (ACE2) inhibiting activity in both groups against ancestral, BA.2 and BA.5 spike proteins (Figure 1G). Peripheral T cell responses were significantly higher in previously-infected individuals against spike S1, S2, and combined membrane and nucleocapsid peptide pools (Figures 1H-J), as previously demonstrated (9).…”

“…Until widespread circulation of omicron, individuals with hybrid immunity were primarily those who were infected during SARS-CoV-2 B.1.1.7/alpha or pre-alpha ('ancestral') waves, prior to commencing their vaccine courses. These 'previously-infected' individuals have higher spike-specific serum antibody and T cell responses after each vaccine dose compared to infection-naive vaccinees (8)(9)(10). Hybrid immunity generated by post-vaccination infections may be quantitatively and qualitatively different from responses seen in individuals who experienced SARS-CoV-2 infection before receiving a vaccination course.…”

Evaluation of post-vaccination immunoglobulin G antibodies and T-cell immune response after inoculation with different types and doses of SARS-CoV-2 vaccines: A retrospective cohort study

“…In this study, more participants with a T-cell response were within the first 2 weeks after their last vaccine dose, and significantly more participants who had no T-cell response were more than 1 month after their last vaccine dose. This seems to contradict what has been previously reported in studies where T-cell responses were better 6 months following vaccination (30), and T-cell responses decline at a slower rate than the antibody levels (31). However, investigating the variation in T-cell response according to the number and type of vaccine doses, populations boosted with one or two doses or those who received an inactivated whole virus vaccine type (BBIBP-CorV) and subsequently boosted with BNT162b2 vaccine were more likely to maintain T-cell response than their counterparts.…”

Prior SARS-CoV-2 infection enhances and reshapes spike protein–specific memory induced by vaccination

“…For example, convalescent individuals develop much higher titers of binding and neutralizing spike protein-specific antibodies (Abs) after mRNA vaccine (5,6) or adenoviral-based vaccine (7,8) than naïve individuals. This so-called "hybrid" immunity is associated with stronger memory B and T cell antiviral responses (9) with better neutralizing Abs (10) and with a lower risk of SARS-CoV-2 reinfection (11)(12)(13)(14).…”