BIVALENT VARIANT mRNA VACCINE BOOSTERS FOR SARS-CoV-2

Candotto V. Bivalent variant mRNA vaccine boosters for SARS-CoV-2 . International Journal of Infection. 2023;7(2):32-34.

V. Candotto*

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.

*Correspondence to:
Valentina Candotto,
Department of Biomedical, Surgical and Dental Sciences,
University of Milan, Milan, Italy..
e-mail: candottovalentina@gmail.com

Received: 29 June, 2023 Accepted: 25 August, 2023

ISSN 1972-6945 [online] Copyright 2023 © by Biolife-publisher This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

KEYWORDS: SARS-CoV-2, bivalent, variant, mRNA, vaccine, booster, Type I interferon

INTRODUCTION

On March 11, 2020, given the global spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the World Health Organization (WHO) declared a pandemic. Understanding and managing SARS-CoV-2 and COVID-19 remains critical as the virus continues to evolve and affect global populations (1). SARS-CoV-2 vaccines have provided immunity against COVID-19, which has caused millions of deaths worldwide. There are different types of vaccines but the one that is the most widely used and effective is the mRNA vaccine (2). mRNA vaccines stimulate the viral protein in the body, causing the release of specific antibodies that are fundamental for combating SARS-CoV-2 viral infection. Bivalent variant boosters in mRNA vaccination provide immunity against various SARS-CoV-2 variants, including Omicron variants.

DISCUSSION

Bivalent variant vaccines are very important in strengthening the immune response against Omicron variants to avoid serious infection (3). Bivalent variant vaccines enhance the immune response and are often administered as booster doses to subjects who have already completed the primary vaccination cycle against COVID-19.

Bivalent variant boosters against the SARS-CoV-2 Omicron subvariants BA.4 and BA.5, as well as the ancestral strain, are only recommended for certain population subsets (4). However, there is increasing evidence to support its administration to the entire population. Davis-Gardner and colleagues, as well as others, found that bivalent boosters had better immunogenicity against emerging variants, including BQ.1.1 and XBB.1, compared to monovalent boosters. COVID-19 has had an enormous impact on the entire population and has resulted in more than 7,500 hospitalizations and 1,100 deaths in the United States among people aged 18 to 49 between September and December of 2022 alone, according to the Centers for Disease Control and Prevention (5).

Several studies indicate that bivalent boosters are clinically effective in reducing the incidence of symptomatic disease, hospitalization, and death in all age groups, including people aged 18 to 49 who have been previously vaccinated (6). Given the excellent safety profile of the vaccines, which is similar to that of the flu vaccine for people aged 6 months and older, the totality of available evidence supports vaccinating all currently eligible people with updated COVID-19 vaccines as an important public health intervention. A bivalent vaccine containing the ancestral SARS-CoV-2 strain plus the BA.4 and BA.5 subvariants had better immunogenicity than the monovalent ancestral booster against BQ.1.1 and XBB.1 (7). Specifically, this bivalent vaccine resulted in levels of neutralizing antibodies against BA.1.1 and XBB.1 that were 1.5 times and 2.6 times greater, respectively, than those that were observed with use of the monovalent booster. None of these increases, however, are likely to be clinically significant.

The major vaccine producers found that a bivalent booster vaccine containing BA.1 that induced a level of neutralizing antibodies that was higher than that with the monovalent vaccine by a factor of 1.75, did not result in significantly better protection against COVID-19 in two prospective, randomized, controlled studies. It has been noted that bivalent boosters have greater protection against disease symptoms in young people aged 18 to 49, at least in the short term (8). However, the protection against hospitalization offered by bivalent boosters, which is the target of this vaccine, was limited to people over the age of 65 years, with a mean age of 76.5 years. The booster administration should be targeted to groups who are more likely to be hospitalized, particularly older or immunocompromised individuals, those who have multiple coexisting conditions, or pregnant women.

Long COVID is an often-debilitating disease that occurs in at least 10% of SARS-CoV-2 infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the disease; Furthermore, similarities with other viral onset diseases such as myalgia, encephalomyelitis, chronic fatigue syndrome, and postural orthostatic tachycardia syndrome have laid the foundation for research in the field. Current diagnostic and therapeutic options are insufficient, and clinical trials that address key hypotheses must be prioritized in order further understand long COVID. To strengthen long COVID research, future studies must account for SARS-CoV-2 testing biases and issues, be based on viral onset research, be inclusive of marginalized populations, and meaningfully engage patients throughout the research process.

IFN type I

Type I interferon (IFN), which includes IFN-α and IFN-β, is a cytokine of innate immunity that is activated by viral infection and plays an important role in COVID-19. After SARS-CoV-2 infection, the immune system recognizes the viral RNA and triggers the production of IFN-I (9). This antiviral cytokine helps fight the replication and spread of SARS-CoV-2 by inducing IFN-I-stimulating genes that counteract the viral cycle. IFN-I plays a dual role in COVID-19 by providing early antiviral defence and modulating the immune response. IFN-I deficiency can lead to uncontrolled viral replication and severe disease, which is seen in patients with severe COVID-19. Certain genetic mutations affecting IFN-I signaling pathways can predispose individuals to severe COVID-19 (10). Additionally, some patients with severe COVID-19 have been found to have autoantibodies against IFN-I, which block its action and lead to poor outcomes.

In 2006, autoantibodies that neutralize IFN-I due to rare inborn errors of T cell tolerance were discovered but were not initially linked to any viral disease. Hereditary and/or autoimmune deficiencies of IFN-I immunity account for approximately 15-20% of cases of critical COVID-19 pneumonia in unvaccinated individuals. Therefore, insufficient IFN-I immunity early in SARS-CoV-2 infection may be a general determinant of progression to life-threatening disease (11).

However, the therapeutic use of IFN-I in viral diseases, including SARS-CoV-2, requires careful consideration of timing, dosage, and patient status to avoid serious side effects. It has been confirmed in the literature show that IFN-I activates natural killer (NK) cells, macrophages and dendritic cells, improving their ability to respond to infection. In addition, IFN-I also aids the maturation of dendritic cells and the subsequent activation of T cells, bridging innate and adaptive immune responses. However, treatment with IFN-I in patients with COVID-19 has given conflicting results because when this cytokine is given at non-physiological doses, it can induce serious inflammation that overlaps with the that induced by SARS-CoV-2. The correct therapeutic use of IFN-I against SARS-CoV-2 infection could be a good strategy to save lives.

CONCLUSIONS

After administration, bivalent variant vaccine boosters increase the level of neutralizing antibodies against different SARS-CoV-2 variants and enhance the immune response. Bivalent boosters are part of a large global vaccination campaign and are especially recommended for high-risk individuals such as immunocompromised people, patients with pre-existing serious conditions, and the elderly. The therapeutic use of IFN-I in patients affected by COVID-19 must be taken into consideration with caution as this cytokine stimulates the innate immune system but is also highly inflammatory with consequences that can be very serious.

Conflict of interest                                                                                                                     

The author declares that they have no conflict of interest.

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