TAG-CO-VAC: WHO Technical Advisory Group on COVID-19 Vaccine Composition Discuss the Omicron Challenges

In an interim statement, the TAG-CO-VAC emphasized that all SARS-CoV-2 Variants of Concern (VOCs), including Omicron, remained to provide substantial levels of protection against severe disease. However, the TAG-CO-VAC understood that it was possible that the efficacy of vaccinations based on the index virus would wane with time due to the antigenic distance and uncertainty of subsequent viral development. Because Omicron is the most antigenically distinct SARS-CoV-2 variant to date, the TAG-CO-VAC advised vaccine producers and regulatory agencies to update the vaccine’s antigen composition by including it for administration as a booster dose.

This includes several bivalent mRNA-based vaccines that contain earlier Omicron descendent lineages in addition to the index virus (i.e., index virus + BA.1 or BA.4/5), which have been approved for emergency use by regulatory authorities. Multiple vaccine manufacturers have created COVID-19 vaccines with an updated antigenic composition.
The TAG-CO-VAC met once more on March 16–17, 2023, in Muscat, Oman. The meeting’s dual objectives were to evaluate the data on the efficacy of updated COVID-19 vaccinations that include Omicron’s ancestors as a booster dose as well as to set deadlines for COVID-19 vaccine composition recommendations in 2023.

The TAG-CO-VAC examined the following data to evaluate the efficacy of updated COVID-19 vaccines that included descendent lineages of Omicron: (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 information on the size and breadth of cross-reactive immune responses aga; and (3) data on the incidence of. The annex that comes with this report contains more information on the evidence that the TAG-CO-VAC considered.

Booster doses of index virus-based vaccinations continue to offer excellent levels of protection against severe illness and death brought on by all SARS-CoV-2 variations, including modern Omicron descendant lineages, according to the TAG-CO-VAC‘s analysis of the data mentioned above. The efficacy of bivalent mRNA vaccines and index virus-based vaccinations against severe disease and symptomatic infection decreases over time. However, immunity against serious illness lasts longer than immunity to symptomatic infection. Booster doses of bivalent mRNA vaccines containing BA.1 or BA.4/5 may somewhat improve vaccine efficiency against symptomatic sickness in comparison to index virus-based vaccines, and similar estimates of vaccine effectiveness are seen in the few studies analyzing severe outcomes.

In comparison to the index virus-based vaccinations, bivalent mRNA vaccines containing both BA.1 and BA.4/5 increase the amplitude and elicit a wider range of cross-reactive immune responses to SARS-CoV-2 variants.
When administered as a booster dose, bivalent mRNA vaccinations containing BA.4/5 produced stronger neutralizing antibody titres against recent descendent lineages of Omicron (BQ.1, XBB.1) than vaccines containing BA.1 did.

Immunological imprinting—also known as original antigenic sin—occurs with repeated exposure to the same antigen and is a phenomena in which immunological memory recall biases the immune response towards previously encountered antigens. Due to a lack of information and the potential for bias, the clinical significance of immunological imprinting in observational epidemiological investigations is yet unknown.
In light of the ongoing SARS-CoV-2 evolution, it is still prudent to pursue broader cross-reactive vaccine-induced immune responses, as the TAG-CO-VAC had advised in its statement released in June 2022.

The TAG-CO-VAC will discuss vaccine antigen composition at next meetings, including a determination of whether future vaccine formulations should contain the index virus. Following their subsequent meeting in May 2023 (see below), the TAG-CO-VAC will offer additional recommendations on any modifications.
Access to vaccines with updated antigen compositions must be guaranteed on an equal worldwide basis.
TAG-CO-VAC continues to support the advancement of vaccines that boost mucosal immunity since they could increase defenses against contracting and spreading SARS-CoV-2.

While recommendations on vaccination practices are made by the Strategic Advisory Group of Experts on Immunization (SAGE), the most recent SAGE recommendations on COVID-19 boosters can be found here. 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.

The COVID-19 vaccine antigen composition revisions will be discussed at future TAG-CO-VAC meetings when the evidence is evaluated. In order to do this, the TAG-CO-VAC intends to meet again twice in 2023: first in May 2023 and one again, around six months later. The performance of vaccine products against circulating SARS-CoV-2 variations, the implications for the antigen composition of the COVID-19 vaccine, and the genetic and antigenic evolution of SARS-CoV-2 variants will also be evaluated at each meeting.

A recommendation will be made based on this evaluation as to whether the current vaccine composition should be maintained or updated. Given the kinetics of vaccine-derived immunity and the requirement for ongoing monitoring of the evolution of SARS-CoV-2, this frequency of the evidence review by TAG-CO-VAC has been proposed; it will be altered if and as necessary.


The Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) is an independent group of experts that periodically reviews the evidence and analyses the implications of emerging VOCs on the performance of COVID-19 vaccines.

The WHO may then receive recommendations from TAG-CO-VAC regarding modifications to vaccine composition that are based on the principles of equitable access and global public health.

An important mechanism for a thorough review and well-coordinated response to the pandemic situation and post-pandemic is information sharing and cross reporting among WHO expert committees, such as the Expert Committee on Biological Standardization (ECBS), the Strategic Advisory Group of Experts on Immunization (SAGE), the Strategic and Technical Advisory Group for Infectious Hazards (STAG-IH), and the Technical Advisory Group on SARS-CoV-2 Virus Evolution (TAG-VE). Thus, current activities on vaccine efficacy and active surveillance of the safety of licensed COVID-19 vaccines are taken into account in this collaborative endeavor.

About Omicron

Omicron is a highly mutated variant of the SARS-CoV-2 virus, which causes COVID-19. It was first identified in South Africa in November 2021 and has since spread rapidly to other countries.

One of the key features of the Omicron variant is that it has a large number of mutations in the spike protein of the virus. This is the part of the virus that allows it to enter human cells, and the mutations in Omicron are thought to make it more transmissible and potentially able to evade some of the immunity conferred by vaccination or previous infection.

The WHO has classified Omicron as a “variant of concern” due to its potential to spread rapidly and cause severe disease. However, it is important to note that more research is needed to fully understand the characteristics and impact of the Omicron variant.

Public health authorities around the world are closely monitoring the situation and taking measures to prevent the spread of Omicron, including travel restrictions, increased testing and tracing, and booster vaccination campaigns. It is important for individuals to continue following public health guidelines, such as wearing masks and practicing physical distancing, to help reduce the spread of the virus.

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