Report of the meeting of the WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) held on 16-17 March 2023


In June 2022, the TAG-CO-VAC published an interim statement highlighting that index virus-based vaccines continued to confer high levels of protection against severe disease caused by all SARS-CoV-2 Variants of Concern (VOCs), including Omicron. However, given the antigenic distance and uncertainties of further viral evolution, the TAG-CO-VAC recognized that it was likely that the effectiveness of vaccines based on the index virus would reduce over time. The TAG-CO-VAC therefore advised vaccine manufacturers and regulatory authorities to consider an update of vaccine antigen composition by including Omicron, as the most antigenically distinct SARS-CoV-2 variant thus far, for administration as a booster dose. Multiple vaccine manufacturers have developed COVID-19 vaccines with an updated antigenic composition; this includes several bivalent mRNA-based vaccines containing earlier Omicron descendent lineages, in addition to the index virus (i.e., index virus + BA.1 or BA.4/5), which have been authorized for emergency use by regulatory authorities.

On 16-17 March 2023, the TAG-CO-VAC reconvened in Muscat, Oman. The purpose of the meeting was two-fold: to review the evidence on the performance of updated COVID-19 vaccines that incorporate descendent lineages of Omicron as a booster dose; and to establish timelines for COVID-19 vaccine composition recommendations in 2023.

The evidence reviewed by the TAG-CO-VAC to assess the performance of updated COVID-19 vaccines that incorporated descendent lineages of Omicron included: (1) published observational epidemiological studies of estimates of absolute and relative vaccine effectiveness of BA.1- or BA.4/5-containing bivalent mRNA vaccines used as a booster dose against symptomatic and severe disease; (2) laboratory-based data on the magnitude and breadth of cross-reactive immune responses against previous and circulating SARS-CoV-2 variants induced by BA.1- or BA.4/5- containing mRNA vaccines, as compared to index virus-based vaccines, used as a booster dose; and (3) laboratory-based studies and observational data on immune memory responses to evaluate the impact of repeated antigen exposure on vaccine-induced immunity and protection. Further details on the evidence reviewed by the TAG-CO-VAC can be found in the accompanying annex.

Based on the review of the data described above, the TAG-CO-VAC concludes:


Booster doses of index virus-based vaccines continue to confer high levels of protection against severe disease and death caused by all SARS-CoV-2 variants, including contemporary Omicron descendent lineages.

Protection from severe disease and symptomatic infection induced by index virus-based vaccines and BA.1- or BA.4/5-containing bivalent mRNA vaccines declines over time. However, protection from severe disease is maintained longer than protection from symptomatic infection.

As compared to index virus-based vaccines, booster doses of BA.1- or BA.4/5-containing bivalent mRNA vaccines may modestly increase vaccine effectiveness against symptomatic disease, while the small number of studies assessing severe outcomes show similar estimates of vaccine effectiveness.

Both BA.1- and BA.4/5-containing bivalent mRNA vaccines enhance the magnitude and elicit greater breadth of cross-reactive immune responses to SARS-CoV-2 variants when used as a booster dose, as compared to the index virus-based vaccines.

BA.4/5-containing bivalent mRNA vaccines induced higher neutralizing antibody titres against recent descendent lineages of Omicron (BQ.1, XBB.1) as compared to BA.1-containing bivalent mRNA vaccines, when used as a booster dose.

There is in vitro evidence to show that immune imprinting, also known as original antigenic sin ? a phenomenon in which immune memory recall biases the immune response towards previously encountered antigen ? occurs with repeated exposure to the same antigen. However, the clinical impact of immune imprinting in observational epidemiological studies to date is unclear, due to limited data and the possibility of bias.

As previously recommended by the TAG-CO-VAC in its statement published in June 2022, achieving broader cross-reactive vaccine-induced immune responses remains prudent in the context of continued SARS-CoV-2 evolution.

In upcoming meetings of the TAG-CO-VAC, vaccine antigen composition will be considered, including an assessment as to whether the inclusion of the index virus is warranted in future vaccine formulations. Further recommendations on any updates will be issued by the TAG-CO-VAC following their next meeting in May 2023 (see below).

For any vaccine product with an updated antigen composition, it is imperative that equitable global access is ensured.

TAG-CO-VAC continues to encourage the further development of vaccines that enhance mucosal immunity because they may improve protection against infection and transmission of SARS-CoV-2.

The role of the TAG-CO-VAC is to recommend whether updates to vaccine composition are needed so that they continue to safely provide protection against SARS-CoV-2 variants; while recommendations on vaccination policies are issued by the Strategic Advisory Group of Experts on Immunization (SAGE); the latest SAGE recommendations on COVID-19 boosters can be found here.

The TAG-CO-VAC will continue to meet to assess the evidence to inform COVID-19 vaccine antigen composition updates. To this end, the TAG-CO-VAC plans to reconvene twice in 2023: once in May 2023 and again, approximately 6 months later. At each meeting the genetic and antigenic evolution of SARS-CoV-2 variants, the performance of vaccine products against circulating SARS-CoV-2 variants and the implications for COVID-19 vaccine antigen composition will be assessed. Based on this assessment, recommendations to either maintain current vaccine composition or to consider updates will be issued. This frequency of the evidence review by TAG-CO-VAC has been proposed given the kinetics of vaccine-derived immunity and the need for continued monitoring of the evolution of SARS-CoV-2, and will be adjusted if and as needed.


Source: WHO

DAte: 2023-04-14

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