The World Health Organization (WHO), has established the Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) to review and assess the public health implications of emerging SARS-CoV-2 Variants of Concern (VOC) on the performance of COVID-19 vaccines and to provide recommendations to WHO on COVID-19 vaccine composition, as needed.
In the context of the circulation of Omicron SARS-CoV-2 Variant of Concern, the TAG-CO-VAC urges broader access globally to current COVID-19 vaccines for primary series and booster doses, in the hope that this also mitigates the emergence and impact of new VOCs.
The TAG-CO-VAC is considering the strain composition of COVID-19 vaccines, and encourages vaccine developers to gather data on a small scale on the breadth and magnitude of immune response for monovalent and multivalent vaccines against VOCs – this data would then be considered in a broader decision-making framework on vaccine composition by the TAG-CO-VAC.
Since its emergence, the SARS-CoV-2 virus has continued to evolve and WHO has designated five variants as SARS-CoV-2 Variants of Concern (VOC) to date – namely Alpha, Beta, Gamma, Delta and Omicron – due to their impact on transmission, disease severity, or capacity for immune escape. While the Omicron variant is spreading rapidly across the world, the evolution of SARS-CoV-2 is expected to continue and Omicron is unlikely to be the last VOC.
The TAG-CO-VAC is developing a framework to analyze the evidence on emerging VOCs in the context of criteria that would trigger a recommendation to change COVID-19 vaccine strain composition and will advise WHO on updated vaccine compositions, as required. This framework considers the global spread and transmissibility, clinical severity, genetic, antigenic and phenotypic characteristics of the VOC, including capacity for immune escape and assessments of vaccine effectiveness.
With available COVID-19 vaccines, the current focus remains on reducing severe disease and death, as well as protecting health systems. Vaccines that have received WHO Emergency Use Listing, across several vaccine platforms, provide a high level of protection against severe disease and death caused by VOCs.
For the Omicron variant, the mutational profile and preliminary data indicate that vaccine effectiveness will be reduced against symptomatic disease caused by the Omicron variant, but protection against severe disease is more likely to be preserved. However, more data on vaccine effectiveness, particularly against hospitalization, severe disease, and death are needed, including for each vaccine platform and for various vaccine dosing and product regimens.
The TAG-CO-VAC will consider a change in vaccine composition:
- to ensure that vaccines continue to meet the criteria established in WHO’s Target Product Profile for COVID-19 vaccines, including protection against severe disease
- to improve vaccine-induced protection.
To that aim, COVID-19 vaccines need to:
- be based on strains that are genetically and antigenically close to the circulating SARS-CoV-2 variant(s);
- in addition to protection against severe disease and death, be more effective in protection against infection thus lowering community transmission and the need for stringent and broad-reaching public health and social measures;
- elicit immune responses that are broad, strong, and long-lasting in order to reduce the need for successive booster doses.
- In line with this approach, there are many options to consider:
- a monovalent vaccine that elicits an immune response against the predominant circulating variant(s), although this option faces the challenge of the rapid emergence of SARS-CoV-2 variants and the time needed to develop a modified or new vaccine;
- a multivalent vaccine containing antigens from different SARS-CoV-2 VOCs;
- a pan SARS-CoV-2 vaccine: a more sustainable long-term option that would effectively be variant-proof.
In the interim, the TAG-CO-VAC encourages COVID-19 vaccine manufacturers to generate and provide data on performance of current and Omicron-specific COVID-19 vaccines, including the breadth, magnitude, and durability of humoral and cell mediated immune responses to variants through monovalent and/or multivalent vaccines. These data will be considered in the context of the framework mentioned above to inform the TAG-CO-VAC decisions when changes to vaccine composition may be required. It would be important for vaccine manufacturers to take steps in the short-term for the development and testing of vaccines with predominant circulating variants and to share these data with the TAG-CO-VAC and other relevant WHO expert committees. Vaccine manufacturers are also encouraged to provide such data for any novel and broadly reactive SARS-CoV-2 vaccines that are developed.
The TAG-CO-VAC will continue to assess evidence on the predominant circulating VOC(s) with respect to properties of spread/transmissibility, clinical severity (virulence), genetic, antigenic and phenotypic characteristics of the VOC, including capacity for immune escape and assessments of vaccine effectiveness and impact, and information provided by manufacturers. The TAG-CO-VAC will then advise WHO on COVID-19 vaccine strain composition, which could potentially be developed either as a monovalent vaccine with the predominant circulating variant or a multivalent vaccine derived from different variants.