The long-term impact of prior SARS-CoV-2 infection on immune responses after COVID-19 vaccination

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Despite evidence relating effectiveness of the current crop of vaccines used against coronavirus disease 2019 (COVID-19) in clinical trials as well as post-marketing surveillance data, its efficacy in the real world is influenced by various factors, namely – demographics of the population, circulating variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), time since vaccination, and vaccination protocols.

Study: Impact of SARS-CoV-2 infection on vaccine-induced immuneresponses over time. Image Credit: D-VISIONS/Shutterstock

A third (booster) vaccination dose is now being administered due to the growing risks of breakthrough infections. With more and more people getting infected, vaccination post-SARS-CoV-2 infection is likely to be commonplace.

Responses to the vaccines have been positively influenced by previous SARS-CoV-2 infection; however, the long-term effects remain unknown. Therefore, it is vital to examine the immune response duration and long-term impacts of SARS-CoV-2 infection, before vaccination, on responses induced by vaccines in real-world evidence studies.

The study

The study published in Clinical & Translational Immunology aimed to determine the impact of prior infection from SARS-CoV-2 infection on immune responses after COVID-19 vaccination in the long term.

Blood samples were collected longitudinally from the COMMUNITY (COVID-19 Immunity) study to determine the binding (WHO BAU mL-1) and neutralizing antibody titers against ten SARS-CoV-2 variants over seven months. All samples were collected after administering BNT162b2 (Comirnaty, Pfizer-BioNTech) in 118 SARS-CoV-2-recovered and 289 SARS-CoV-2-naive healthcare workers who had previous exposures to SARS-CoV-2. 

Additionally, another group of people was followed—47 with prior and 60 without prior SARS-CoV-2 infection—for three months after administering the ChAdOx1 nCoV-19 vaccine (Vaxzevria, AstraZeneca). T-cell responses specific to SARS-CoV-2 were studied in these vaccine recipients who were either SARS-CoV-2-naive or SARS-CoV-2-recovered.


This study reported a striking increase in immune responses – both humoral and cellular, to vaccination following prior SARS-CoV-2 infection. It also reported higher neutralizing potency and coverage against SARS-CoV-2 variants in comparison to individuals who were SARS-CoV-2 naive.

Following ChAdOx1 nCoV-19 and BNT162b2 vaccinations, a remarkable decline was recorded during the initial month for BAU mL1 and pseudo-neutralizing antibody titers. Markedly lower titers were noted on immunization with ChAdOx1 nCoV-19 as compared to BNT162b2 – these findings support the recommendation of booster doses and planning SARS-CoV-2 vaccine programs.

As previously reported, it was further substantiated that T-cell responses and antibody titers remained significantly increased over three months after ChAdOx1 nCoV-19 and for seven months after BNT162b2—among healthcare workers with mostly mild SARS-CoV-2 infections before vaccination. This shows that the effect of the previous infection on the immune response post vaccination is not temporary. The memory compartment seems to be constantly evolving after both infection and vaccination but to a lesser increase in the widespread immunity post-vaccination.

In addition, vaccinees who recovered from SARS-CoV-2 showed a higher development of neutralizing antibody responses against SARS-CoV-2 variants. This finding suggests that SARS-CoV-2-recovered immune-competent vaccinees elicit better cellular responses than SARS-CoV-2-naive vaccinees.

The results indicate that the decline in antibody titers in a portion of individuals three-to-seven months post the second dose of the COVID-19 vaccine necessitates a third booster dose in a small portion of the vaccinated population. Of note, these evaluations were carried out during the period of the Alpha variant, and these titers are likely to yield lower efficacy against the Delta variant.

A significant difference was observed between three-to-four weeks and six-to-eight weeks for pseudo neutralization in SARS-CoV-2-naive participants. This suggested an improved memory formation in the latter group. It was also found that a longer duration between SARS-CoV-2 infection and COVID-19 vaccination increased the neutralizing potency and immune coverage.

Further studies are required to assess any potential differences in the longevity of immunological memory. This research had its limitations as it was observational, single-center, and included only healthcare workers – wherein most women were of working age. The antibody trajectory may differ in the elderly and settings devoid of repeated viral encounters.


Here, enhanced cellular immune responses, antibody titers, and neutralizing coverage potential in vaccinees with previous SARS-CoV-2 infection were compared to vaccinees without previous SARS-CoV-2 infection. The results revealed that prior infection accentuated these effects after vaccination.

Therefore, prior SARS-CoV-2 infections should be kept in mind while making vaccination policies, planning booster doses, and designing COVID-19 vaccination programs, both at present and in the future.

Source: News Medical

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