Updated COVID-19 Vaccines against New Circulating Variants - The Essentials

Introduction:

Since COVID-19 (coronavirus disease) was declared a global pandemic by the World Health Organization (WHO), seamless research intensified the testing of several vaccine candidates that could offer immunity against the deadly disease. By 2021, scientists and pharmaceutical companies will have developed a prime set of FDA (Food and Drug Administration)-approved COVID-19 vaccines available for human use. These vaccines effectively and safely prevented SARS‑CoV‑2 (severe acute respiratory syndrome coronavirus 2) infection.

However, the mutational (ability to change genetic composition) potency of SARS‑CoV‑2 led to the emergence of new variants (Omicron variant). The recommended vaccines showed reduced efficacy against these newly circulating variants, leading to increased COVID-19 hospitalizations. The USFDA (United States Food and Drug Administration) instructed the biopharma companies to redesign the COVID-19 vaccines that could provide enhanced protection against emerging variants.

By the end of September 2023, the FDA designed and authorized new vaccine shots for clinical use. These newly designed vaccines are termed updated (2023–2024 Formula) vaccines, and this article divulges its details.

What Are Newly Circulating Coronavirus Variants?

SARS‑CoV‑2 is a novel coronavirus strain. Its genome contains a single-stranded RNA that undergoes spontaneous mutations and is enclosed in a viral envelope containing highly antigenic spike proteins.

Some of the salient features of coronavirus variants are as follows:

• Genetic variations lead to circulating new viral strains called lineages. The change in genetic component impacts the viral properties like transmission and disease severity.

• The WHO characterizes these new viruses as variants of interest (VOIs) for lineages with less infectivity and as variants of concern (VOCs) if the new strain is increasingly contagious.

• The novel strain that started the pandemic was designed as Alpha, and subsequent variants were named Beta and Delta. However, these variants have been replaced by new strains.

• Omicron (BA.1) strain emerged as a more stable variant, and its subvariants were found to predominate for nearly two years in countries like the United States.

• It is evident that the original BA.1 (Omicron) variant is not circulating anymore. Its subvariants are now found to be detected in circulation.

• In early 2023, the EG.5 (Eris) strain became dominant in countries like the United States, and by mid-year, another subvariant BA.2.86 (Pirola) had emerged.

Why Are Updated COVID-19 Vaccines Needed?

The potential benefits and efficacy of COVID-19 (bivalent mRNA) vaccines have been consistently monitored by the ACIP (Advisory Committee on Immunization Practices) since June 2020. Using the GRADE (grading of recommendations, assessment, development, and evaluation) methodology, the immunogenicity, effectiveness, safety, and potential risks of COVID-19 vaccines were systematically reviewed.

The evaluated data from ACIP anticipated that all existing vaccine formulations need to be updated for the following reasons:

• Mutations change the antigenicity of spike proteins, resulting in numerous variants that affect the immunogenicity of the vaccines.

• The effectiveness of existing (bivalent mRNA) COVID-19 vaccines, which once protected against SARS‑CoV‑2 strains, started waning in efficacy against new emerging subvariants resulting in increased COVID-19-associated illnesses.

• Although these variants do not cause major outbreaks, they lead to considerable morbid complications and progressive mortality rates.

• Elderly people (above 65 years) and infants (below six months) were more prone to COVID-19 infection and at higher risk of developing complications.

• Immunocompromised individuals and patients with chronic illness (diabetes, heart disease) are at a higher risk of developing severe illness or comorbid conditions.

• The risk of COVID-19 illness continues in healthy individuals (six months to 64 years) as the infection causes long-term health problems.

What Are the Updated COVID-19 Vaccines?

Omicron XBB subvariants started dominating in 2023, and the FDA, based on ACIP data, suggested that pharmaceutical companies and the research fraternity redesign the existing vaccine formulations to target the XBB lineage. The COVID-19 vaccines were reformulated and updated to target recent circulating variants accurately and were authorized and approved by USFDA under emergency use authorization (EUA) by September 2023.

The updated (2023–2024 Formula) vaccines for COVID-19 that are currently available are listed below:

• A single monovalent component targeting the XBB.1.5 Omicron variant has been included in all the updated vaccines.

• This XBB.1.5 monovalent component gives broader vaccine-mediated immunity and effectively protects against circulating XBB subvariants, thereby reducing severe COVID-19-related complications.

• mRNA monovalent vaccines reformulated by Pfizer-BioNTech and Moderna were the first updated COVID-19 vaccines approved by the FDA.

• Later, the Novavax COVID-19 Vaccine, an adjuvanted monovalent vaccine targeting spike protein present in XBB.1.5 omicron sublineage, was also updated and authorized under EUA by the FDA.

• Clinical studies show that the updated vaccines' neutralization efficacy is effective against current circulating subvariants (EG.5 and BA.2.86) of COVID-19.

What Are the Recommendations for the Updated COVID-19 Vaccines?

The CDC (Centers for Disease Control and Prevention) and FDA have exclusively published the following recommendations for vaccination using updated (2023–2024 Formula) COVID-19 vaccines.

• The global regulatory bodies recommend that these updated 2023–2024 vaccine formulas contain monovalent targeting XBB.1.5 components that are evident in circulating subvariants.

• The FDA has assessed the safety and efficacy of these authorized updated vaccines through risk-benefit assessment, and it has been documented that the potential benefits outweigh the risks of these vaccines in eligible individuals (six months of age and above).

• These vaccines are recommended for immunocompromised (moderate to severe) individuals who have fully completed the previous COVID-19 vaccine series under guided clinical judgment from healthcare providers.

• The previously existing bivalent boosters of COVID-19 vaccines are no longer recommended for circulating Omicron subvariants.

• Pfizer-BioNtech and Moderna Updated COVID-19 Vaccines -

  • These monovalent vaccines are recommended for individuals aged more than or equal to 12 years.

  • These vaccines are also recommended for children from six months to 11 years under guidelines following emergency use authorization (EUA).

  • Regardless of any previous history of COVID-19 vaccination, individuals five years of age and above are authorized to receive a single updated mRNA vaccine dose at two months from the last COVID-19 vaccination.

  • Individuals from six months to four years with previous COVID-19 vaccination can receive one to two updated mRNA doses depending on the number and duration of previously received vaccination.

  • Unvaccinated persons aged six months to four years are eligible for three updated and authorized Pfizer-BioNTech vaccine doses and two authorized Moderna vaccine doses.

• Novavax Updated Vaccine -

  • This vaccine is authorized under EUA for individuals aged 12 years and above.

  • Individuals aged 12 years and above with a previous COVID-19 vaccination history are eligible for a single dose, whereas two doses are recommended for unvaccinated individuals.

  • The original Novavax monovalent COVID-19 vaccine is not authorized anymore for use in countries like the United States.

Conclusion:

The CDC still recognizes COVID as a major public health threat causing severe respiratory illnesses. The updated (2023-2024 formula) vaccines effectively prevent serious illnesses and hospitalizations that occur due to infections from presently circulating coronavirus subvariants. The updated COVID-19 vaccination represents an affordable and cost-effective intervention in preventing complications due to COVID-19, especially in elderly adults (more than 65 years) who are more prone to the infection. Further, these vaccines are administered by evaluating clinical considerations and following authorized guidelines.