Past infections may shape your COVID booster’s punch against Omicron


In a latest examine printed in Nature Communications, researchers study the impact of an infection and coronavirus illness 2019 (COVID-19) vaccination in wholesome people with various imprinted immunity in opposition to extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Research: Previous immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough infection risk. Picture Credit score: Kateryna Kon /


The continuous emergence of novel SARS-CoV-2 variants, mixed with widespread vaccination charges, straight contributes to the present transmission dynamics of SARS-CoV-2. Actually, the frequency of breakthrough infections (BTIs) in vaccinated people, together with reinfections, is progressively rising, significantly after the emergence of the SARS-CoV-2 Omicron variant and its sublineages. 

A number of components, together with age, gender, comorbidities, and prior an infection historical past, affect humoral and mobile immune responses after vaccination. In consequence, post-vaccination immunity is very heterogeneous throughout people. Thus far, it stays unclear why some people are at an elevated danger of main infections and reinfections, significantly from the Omicron and its subvariants, even after getting vaccinated in opposition to COVID-19.

A number of research have described the idea of immune imprinting, which is the shortcoming of the immune system to mount an efficient response to an infection by a brand new variant or vaccines resembling the unique immunogen for the influenza virus, human immunodeficiency virus (HIV), and SARS-CoV-2. Nonetheless, whether or not the systemic immunoglobulin A (IgA) response is related to safety in opposition to SARS-CoV-2 BTIs stays unknown.

In regards to the examine

Within the present potential observational examine, researchers recruited healthcare professionals from Rigshospitalet and Herlev-Gentofte College hospitals in Denmark. All examine individuals obtained a two-dose main collection and booster dose of the Pfizer-BioNTech BNT162b2 COVID-19 vaccine.

Research individuals supplied venous blood samples at baseline, 21 days, two, six, and 12 months after receiving the primary vaccine dose. An enzyme-linked immunosorbent (ELISA)-based assay was used to quantify IgG and IgA ranges within the plasma. Moreover, the Elecsys® Anti-SARS-CoV-2 assay was used to quantify complete antibodies in opposition to the SARS-CoV-2 nucleocapsid (N) protein, which displays earlier SARS-CoV-2 an infection.

An ELISA-based pseudo-neutralizing assay was used to estimate the inhibitory potential of neutralizing antibodies (nAbs) in opposition to the SARS-CoV-2 receptor-binding area (RBD). Interferon-gamma (IFN-γ) ranges launched from stimulated T-cells in affected person entire blood samples had been additionally measured.

Research findings

The third vaccine dose, often known as a booster dose, resulted in a considerably elevated IgG response to the SARS-CoV-2 RBD. This response was straight associated to the age, intercourse, and an infection standing of the person.

Comparatively, age and gender didn’t affect nAbs ranges following booster vaccination. That is seemingly as a result of antibody affinity maturation happens after the booster dose and is extra pronounced in people with hybrid immunity.

The reinfection price was increased amongst people beforehand contaminated earlier than Omicron at 37.5%, whereas 48.4% of infection-naive people contracted Omicron an infection after booster vaccination. Amongst Omicron-infected people, these sampled after 12 months exhibited considerably decreased ranges of IgG/IgA and nAbs following main vaccination as in comparison with infection-naive people.

Is vaccination or an infection extra protecting?

It stays unclear whether or not immune imprinting in unvaccinated people modulates immunity at vaccine priming, thus necessitating granular information to elucidate in-depth B reminiscence cell responses. However, the examine findings exhibit that people experiencing reinfections had a weaker humoral response, characterised by a decrease peak and marked waning after the vaccine priming.

Earlier research have documented discrepancies concerning the affiliation between IgG and mucosal IgA. Within the present examine, the neutralizing exercise of IgG was seemingly enhanced by vaccination; nonetheless, this antibody response was extra distinguished in beforehand contaminated people. The protecting function of serum IgA, as in comparison with IgG, in opposition to SARS-CoV-2 an infection seems to be short-term and modest. 

Since mobile immunity stays unaltered after vaccination, it’s seemingly accountable for stopping extreme COVID-19 outcomes regardless of being ineffective in opposition to SARS-CoV-2 transmission and BTIs. Accordingly, IFN-γ ranges of vaccinated people experiencing Omicron reinfection and vaccinated people experiencing a main Omicron an infection had been comparable. Certainly, vaccination triggered a sturdy mobile response that was boosted additional after the primary viral publicity.

Though IgA antibodies are the first protection mediator on mucosal surfaces, the researchers of the present examine couldn’t conclusively decide the origin of IgA in circulation and whether or not contaminated and naive people had comparable IgA portfolios.


Pre-existing immunity of a person in opposition to SARS-CoV-2 considerably impacts their humoral and mobile responses after booster vaccination, as demonstrated by a sturdy IgA response noticed in beforehand contaminated people following booster vaccination. Nonetheless, within the present examine, main Omicron an infection and subsequent Omicron reinfection considerably decreased these responses.

Using completely different vaccine boosters, mixed with frequent mutations in novel SARS-CoV-2 variants, has elevated the complexity of immune responses to SARS-CoV-2, which, in flip, complicates future COVID-19 vaccine methods. Thus, continued analysis on immune responses to SARS-CoV-2 is important for the event of latest and efficient vaccines able to eliciting efficient IgA responses.

Journal reference:

  • Pérez-Alós, L., Hansen, C.B., Almagro Armenteros, J.J. et al. (2023). Earlier immunity shapes immune responses to SARS-CoV-2 booster vaccination and Omicron breakthrough an infection danger. Nature Communications 14(5624). doi:10.1038/s41467-023-41342-2
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