Efficacy of COVID-19 vaccines against the omicron variant of SARS-CoV-2

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), is an enveloped virion containing a positive-sense single strand of ribonucleic acid (RNA). Despite having proofreading polymerase activity, the virus has a high mutation rate due to uncontrolled replication in the host. With each infection, mutations accumulate and spread globally through travel and migration. The World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) have identified several variants of concern (VOCs) of SARS-CoV-2, including Alpha, Beta, Gamma, Delta, and Omicron. Unlike a typical ladder paradigm of viral evolution, these VOCs have not descended progressively from each other. The emergence of these variants raises concerns about their impact on diagnostic protocols, disease severity, transmission rates, and vaccine effectiveness. This review discusses the efficacy of COVID-19 vaccines against the Omicron variant and highlights the journey of vaccine development in response to the evolving virus.

The Omicron variant, first identified in late 2021, quickly became the dominant strain globally due to its high transmissibility and ability to evade vaccine-induced immunity. Omicron has multiple sub-lineages, all showing significant resistance to neutralizing antibodies generated by previous infections or vaccinations. This variant's mutations primarily affect the spike protein, the target for most vaccines, reducing their efficacy. Consequently, breakthrough infections and reinfections have become more common.

Initial studies on the efficacy of monovalent vaccines, such as BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), showed high effectiveness in preventing symptomatic and severe COVID-19 disease caused by earlier variants. For instance, these vaccines demonstrated over 90% efficacy against the Alpha variant and maintained high effectiveness against severe outcomes from the Beta variant, despite a reduction in neutralizing antibody titers. However, the advent of the Delta variant saw a decline in vaccine effectiveness to approximately 66%. This decline, coupled with the waning immunity over time and the emergence of the Omicron variant, necessitated additional booster doses to maintain protection against severe disease.

The Omicron variant's emergence significantly impacted the efficacy of existing vaccines. Studies indicated that vaccine effectiveness against Omicron-related hospitalization was reduced to around 70% for those who received the primary two-dose series of BNT162b2. Further, the durability of this protection waned over time, particularly against the BA.1, BA.2, BA.4, and BA.5 sub-lineages of Omicron. By October 2022, the effectiveness of the BNT162b2 vaccine against hospitalization due to these sub-lineages was reduced to 56.3%.

To address the challenges posed by the Omicron variant, updated vaccines, including bivalent boosters, were developed. These bivalent boosters were designed to target both the original virus strain and the Omicron variant, thereby enhancing immune response and providing better protection. Studies have shown that a third or fourth dose of the monovalent vaccine primarily protected against severe disease, with Omicron-specific breakthrough infections still occurring at notable rates.

The introduction of bivalent boosters marked a pivotal development in the fight against Omicron. Research demonstrated that these updated vaccines enhanced immunity and reduced the incidence of breakthrough infections. For example, the administration of a fourth dose of the monovalent mRNA vaccine led to similar seroconversion levels and comparable protection against severe disease caused by Omicron sub-lineages. This underscores the importance of continued vaccination efforts and booster doses to maintain high levels of protection against evolving variants.

Despite the challenges posed by the Omicron variant, vaccination remains a critical tool in controlling the pandemic. Vaccines continue to reduce the severity of COVID-19, lowering hospitalization and mortality rates even as new variants emerge. The ongoing evolution of SARS-CoV-2 underscores the need for continuous monitoring and updating of vaccines to address emerging threats effectively.

In conclusion, the journey from the initial COVID-19 vaccines to the updated bivalent boosters highlights the dynamic nature of the pandemic and the ongoing need for adaptive vaccination strategies. While first-generation vaccines provided critical protection against severe disease and mortality, their efficacy against the highly transmissible and immune-evasive Omicron variant was limited. The development and deployment of bivalent boosters represent a significant advancement, offering enhanced protection and underscoring the importance of booster doses in the ongoing battle against COVID-19 and its variants. Continued research and vaccination efforts remain essential to combat the ever-evolving SARS-CoV-2 virus and ensure public health safety.

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https://www.xiahepublishing.com/2472-0712/ERHM-2023-00023

The study was recently published in the Exploratory Research and Hypothesis in Medicine.

Exploratory Research and Hypothesis in Medicine (ERHM) publishes original exploratory research articles and state-of-the-art reviews that focus on novel findings and the most recent scientific advances that support new hypotheses in medicine. The journal accepts a wide range of topics, including innovative diagnostic and therapeutic modalities as well as insightful theories related to the practice of medicine. The exploratory research published in ERHM does not necessarily need to be comprehensive and conclusive, but the study design must be solid, the methodologies must be reliable, the results must be true, and the hypothesis must be rational and justifiable with evidence.

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