The duel between COVID-19 and mRNA vaccines — what lies ahead?

In the ECCMID 2022 Pfizer Integrated Symposium “The science of mRNA COVID-19 vaccines: paving the way for a new prevention paradigm”, the focus was on reviewing the evolution of the COVID-19 pandemic management so far, as well as preparing for the future. Experts discussed the changing variant landscape, the evidence for booster shots and the potential future scenarios for SARS-CoV-2.

The rationale for boosters

The vaccines against SARS-CoV-2 were developed at an unprecedented speed, and they were a game changer for managing the pandemic from the public health viewpoint. However, SARS-CoV-2 continuously evolves and new variants are emerging. Variants of interest are especially those with mutations in the spike protein, as such mutations could affect the infectiousness of the virus as well as its ability to evade the immune system (Kupferschmidt, 2021).

The rapid emergence of new variants observed with SARS-CoV-2, combined with waning vaccine-induced immunity over time, poses a challenge for pandemic management. A reduction in vaccine protection was observed as the Delta variant started to spread, especially in countries where the interval between the first two doses had been shorter (Figure 1; Goldberg et al., 2021). This gave rise to the need for periodically boosting vaccine induced immunity. Boosters seem to be able to offer enhanced protection beyond the primary vaccination series (Falsey et al., 2021; Mielke et al., 2022; Tartof et al., 2022).
 

Vaccine efficacy in the Omicron era

Omicron is very different from previous SARS-CoV-2 strains. The neutralization capability of currently available vaccines seems to be decreased for this variant (Kupferschmidt, 2021; Muik et al., 2022). Boosters seem to be capable of restoring, although not enhancing, this neutralization capability (Muik et al., 2022). Additionally, there is some evidence that immunity against severe disease is maintained by the adaptive immune system (Gao et al., 2022).

Clinical data from the United Kingdom shows that although vaccine-induced immunity against reinfection is now declining again with the Omicron variant, vaccine efficacy against severe disease and hospitalization seems to remain high in most populations after boosting (Figure 2; UK Health Security Agency, 2021).
 

Future of SARS-CoV-2

Experts forecast that instead of complete eradication of SARS-Cov-2, the virus will likely become endemic. In such a case, immune escape, waning immunity and uneven vaccine distribution would likely be the main drivers of SARS-Cov-2 circulation in the population (Phillips, 2021). Results from a common cold coronavirus show the virus evolves to evade immunity induced by earlier versions of the virus, facilitating reinfection (Eguia, 2021).

The global health threat posed by SARS-Cov-2 in the future depends on several factors, including whether it will retain its virulence and whether there will be reservoirs for zoonotic transmission. Future scenarios also depend on the global vaccine strategy employed today: by aiming for high rates of immunity in the global population and preventing vaccine stockpiling in wealthy countries, the evolution and spread of new variants may be reduced (Figure 3; Wagner, 2022). 
 

ECCMID 2022 References:

Dynamic nature of SARS-CoV-2 variants. Federico Martinón-Torres (Spain). Presented at ECCMID 2022 on 25 April 2022.

The role of boosters in a changing environment. Romina Quercia, Pfizer Employee (United Kingdom). Presented at ECCMID 2022 on 25 April 2022.

Potential public health impact of COVID-19 vaccines at the individual and population level. Itamar Grotto (Israel). Presented at ECCMID 2022 on 25 April 2022.

Additional references:

Comirnaty Summary of Product Characteristics
https://www.ema.europa.eu/en/documents/product-information/comirnaty-epar-product-information_no.pdf. Oppdatert 21.07.2022

Eguia RT, Crawford KHD, Stevens-Ayers T, et al. A human coronavirus evolves antigenically to escape antibody immunity. PLoS Pathog. 2021 Apr 8;17(4):e1009453. doi: 10.1371/journal.ppat.1009453 

Falsey AR, Frenck RW Jr, Walsh EE, et al. SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3. N Engl J Med. 2021 Oct 21;385(17):1627-1629. doi: 10.1056/NEJMc2113468

Gao Y, Cai C, Grifoni A, et al. Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant. Nat Med. 2022 Mar;28(3):472-476. doi: 10.1038/s41591-022-01700-x

Goldberg Y, Mandel M, Bar-On YM, et al. Waning Immunity after the BNT162b2 Vaccine in Israel. N Engl J Med. 2021 Dec 9;385(24):e85. doi: 10.1056/NEJMoa2114228

Kupferschmidt K. Evolving threat. Science. 2021 Aug 20;373(6557):844-849. doi: 10.1126/science.373.6557.844

Mielke N, Johnson S, Bahl A. Boosters reduce in-hospital mortality in patients with COVID-19: An observational cohort analysis. Lancet Reg Health Am. 2022 Apr;8:100227. doi: 10.1016/j.lana.2022.100227

Muik A, Lui BG, Wallisch AK, et al. Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine-elicited human sera. Science. 2022 Feb 11;375(6581):678-680. doi: 10.1126/science.abn7591

Phillips N. The coronavirus is here to stay - here's what that means. Nature. 2021 Feb;590(7846):382-384. doi: 10.1038/d41586-021-00396-2

Tartof SY, Slezak JM, Puzniak L, et al. Effectiveness of a third dose of BNT162b2 mRNA COVID-19 vaccine in a large US health system: A retrospective cohort study. Lancet Reg Health Am. 2022 May;9:100198. doi: 10.1016/j.lana.2022.100198

UK Health Security Agency. SARS-CoV-2 variants of concern and variants under investigation in England Technical briefing: Update on hospitalisation and vaccine effectiveness for Omicron VOC-21NOV-01 (B.1.1.529). 31 December 2021. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1045619/Technical-Briefing-31-Dec-2021-Omicron_severity_update.pdf

Wagner CE, Saad-Roy CM, Grenfell BT. Modelling vaccination strategies for COVID-19. Nat Rev Immunol. 2022 Mar;22(3):139-141. doi: 10.1038/s41577-022-00687-3

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