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Immune response to variants of concern of SARS-CoV-2 after natural infection or vaccination

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A recent review article published in the MDPI journal Virus highlights how available vaccines may be effective in protecting individuals against severe forms of coronavirus disease 2019 (COVID-19), but protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ) and its transmission to others can be reduced – with consequences for community protection and collective immunity.

As a result of infection with SARS-CoV-2, a causative agent of the current COVID-19 pandemic, there is activation of the innate and adaptive immune systems in our bodies. So, in many ways, the severity of the disease depends on how we respond to the infection.

The generated neutralizing antibodies are highly specific for viral epitopes mainly present in the spike glycoprotein of SARS-CoV-2, but T cells are also recruited in order to secrete antiviral cytokines and kill infected cells.

If the host’s early immune response is unable to control and clear the virus, the disease progresses to a secondary phase characterized by an uncontrolled inflammatory response from the host, which is responsible for known serious manifestations and may ultimately lead to severe disease. organ damage.

This is why vaccines have really been a game-changer in this pandemic. Even though we are just over 18 months away from the pandemic, four vaccines are already widely used around the world: BNT162b2 from Pfizer / BioNtech2, mRNA-1273 from Moderna, Ad26.COV2S from Janssen and AstraZeneca’s ChAdOx1.

The genomic structure of SARS-CoV-2.  The genome encodes two large open reading frames (ORF), ORF1a and ORF1b, which encode 16 non-structural proteins (NSP1-NSP16).  Structural genes encode structural proteins, tip (S), envelope (E), membrane (M) and core (N), and accessory genes (3a, 3b, 6, 7a, 7b, 8, 9 and 10) (Created with Biorender.com accessed September 9, 2021).

The genomic structure of SARS-CoV-2. The genome encodes two large open reading frames (ORF), ORF1a and ORF1b, which encode 16 non-structural proteins (NSP1-NSP16). Structural genes encode structural proteins, tip (S), envelope (E), membrane (M) and core (N), and accessory genes (3a, 3b, 6, 7a, 7b, 8, 9 and 10) (Created with Biorender.com accessed September 9, 2021).

A rapid rise in viral variants

However, by the end of 2020 there was already an emergence of several different variants of SARS-CoV-2 of concern (due to mutational changes in the viral genome) that showed increased transmissibility and possible evasion of immune responses generated by previous SARS. -CoV-2 infection.

It should be noted that the variants of concern are strains of SARS-CoV-2 which have higher rates of transmissibility, more severe clinical presentations, poorer response to treatment, or inadequate diagnostic performance with the use of procedures and established tests.

Likewise, these viral variants are also a threat to the effectiveness of vaccines. Due to the presence of mutations in the spike glycoprotein (especially in neutralizing antibody epitopes), laboratory experiments revealed a decreased ability of post-vaccination serum samples to neutralize variants of concern.

The emergence of new variants over time.  The colors represent the ancestral clade.  Variants of concern and variations of interest are shown on the graph.  The image was retrieved from www.nextstrain.org under a CC-BY-4.0 license and is unchanged (accessed July 15, 2021).
The emergence of new variants over time. The colors represent the ancestral clade. Variants of concern and variations of interest are shown on the graph. The image was retrieved from www.nextstrain.org under a CC-BY-4.0 license and is unchanged (accessed July 15, 2021).

The possibility of reinfection

Even though the worrisome variants carry mutations that escape complete neutralization by antibodies, and there are several reports of re-infections, it is still unclear whether the risk of re-infection is actually increased. Theoretically, the risk exists if the spike glycoprotein changes, mainly due to its role in entering cells and because it is targeted by protective antibodies.

Some studies show that this can indeed be the case, but it depends on the variant in question. A UK study proved reinfection in 0.7% of individuals tested, but this did not correlate with the proportion of infections in these regions caused by the alpha variant – indicating a minor effect of this variant on the risk of reinfection.

On the other hand, a longitudinal serological study of unvaccinated repeat blood donors from Manaus in Brazil showed that amid the emergence of the gamma variant, a total of 16.9% of the suspected infections had serological evidence of ” a previous infection with SARS-CoV. -2.

Vaccines and variants of concern

While the effectiveness of vaccines to protect against symptomatic infection with variants of concern may be reduced, there is every reason to conclude that they remain somewhat effective in preventing severe forms of COVID-19, hospitalization and / or dead. It is also known that cellular immune responses remain largely preserved.

Still, at this time, it’s unclear whether variant-specific boosters will be needed in the future. Such booster vaccines could either use the advanced glycoprotein from the original strain of SARS-CoV-2 Wuhan, or that derived from a variant of concern. Data from Israel demonstrate that a third injection during generalized circulation of the delta variant can certainly provide short-term protection against confirmed infection and severe illness.

However, it remains to be seen whether the spike protein will be able to mutate further to evade immune responses while maintaining high levels of infectivity. Along with the kinetics of immune responses, this will ultimately determine whether and how often updated vaccines or boosters will be needed.


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