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