Types of data requested to inform December 2024 COVID-19 vaccine antigen composition deliberations

The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) continues to closely monitor the genetic and antigenic evolution of SARS-CoV-2 variants, immune responses to SARS-CoV-2 infection and COVID-19 vaccination, and the performance of COVID-19 vaccines against circulating variants. Based on these evaluations, WHO advises vaccine manufacturers and regulatory authorities on the implications for future updates to COVID-19 vaccine antigen composition. The next decision-making meeting of the TAG-CO-VAC is scheduled for mid-December 2024, after which a statement on COVID-19 vaccine antigen composition and an accompanying data annex will be published on the WHO website. These meetings are timed to balance the availability of the latest epidemiological, immunological, and virological data, with the kinetics of vaccine-induced protection and the lead time manufacturers need to update the antigen composition of authorized COVID-19 vaccines.

The purpose of this statement is to guide the scientific community and vaccine manufacturers as to which data should be generated ahead of the December 2024 TAG-CO-VAC deliberations.

To inform decisions on COVID-19 vaccine antigen composition,^1-4 the TAG-CO-VAC reviews data (see Table) on the genetic evolution of SARS-CoV-2 and the antigenic characteristics of previously and currently circulating variants. This includes the analysis of naïve animal antisera in one-way and two-way neutralization tests, as well as immunogenicity data that assess the breadth and durability of immune responses, including neutralizing antibody responses, using sera from sequentially immunized or infected animals and pre-and post-vaccination human sera. The TAG-CO-VAC also considers vaccine effectiveness (VE) estimates of currently approved COVID-19 vaccines, particularly those that control for time since vaccination and that provide variant-specific estimates across different vaccine platforms. Further examples of published data reviewed by TAG-CO-VAC and used to inform decisions on COVID-19 vaccine antigen composition can be found in the annexes accompanying each statement.^1-4

In addition, the TAG-CO-VAC reviews available data from vaccine manufacturers, including animal and/or human studies demonstrating the breadth and durability of immune responses elicited by currently authorized vaccines, as well as any vaccine candidates in development. Vaccine manufacturers are also asked to provide observational epidemiological data that demonstrate the efficacy or effectiveness of their authorized COVID-19 vaccines, as well as any vaccine candidates in development.

At this stage, the key antisera and antigens of interest for the December 2024 decision-making meeting for demonstrating breadth include antisera to: BA.2 (other historical reference viruses - e.g., index, Alpha, BA.1 - are also useful for determining antigenic relationships), XBB.1.5, JN.1, KP.2, KP.3.1.1 and emerging SARS-CoV-2 variants. Antisera of interest are animal sera after single or sequential exposure and human sera after boost with monovalent JN.1, KP.2 or XBB.1.5, vaccines. Both pre- and post-vaccination sera should be included and for all antisera, neutralizing antibody titers should be analyzed against at least one variant that emerged after the vaccine antigen, where feasible. Analysis of this antisera against the same panel of virus antigens as well as other new emerging SARS-CoV-2 variants will provide insight into antigenic characteristics of previous and emerging variants. Emerging variants include the list of SARS-CoV-2 Variants of Interest (VOI) and Variants Under Monitoring (VUM) maintained on the WHO website. Relative VE estimates should be calculated during periods of circulation of XBB, JN.1, KP.3.1.1 or other emerging variant(s) in human populations across age groups with separate VE estimates for each of the following vaccine antigen compositions: monovalent JN.1, monovalent KP.2 or monovalent XBB.1.5.

In preparation for the December 2024 meeting, the TAG-CO-VAC encourages the scientific community and vaccine manufacturers to prioritize generating and sharing the data outlined here to ensure evidence-informed deliberations on COVID-19 vaccine antigen composition; please contact the TAG-CO-VAC Secretariat: [[email protected]].

Type of data	Comments
SARS-CoV-2 genetic evolution	Key variants include the list of Variants of Interest (VOI) and Variants Under Monitoring (VUM). This list is maintained on the WHO website.+
Antigenic characterization of previous and emerging SARS-CoV-2 variants	Naïve animal antisera against each of the following: BA.2, XBB.1.5, JN.1, KP.2, KP.3.1.1 and potentially emerging variants* analyzed in one-way and two-way neutralization tests (pseudotype and live virus neutralization assays).
Preliminary immunogenicity data on breadth and durability of immune responses following vaccination or infection with SARS-CoV-2 spike variant antigens.	Neutralization of various representative viruses by non-naïve animal sera (e.g., sequentially immunized or infected), for each of the following antigens: BA.2, XBB.1.5, JN.1, KP.2, KP.3.1.1 + new emerging variants;* Neutralization of various representative viruses (BA.2, XBB.1.5, JN.1, KP.2, KP.3.1.1 + emerging variants*) by both pre- and post-vaccination human sera. Vaccinee sera should be analyzed in priority order: JN.1, KP.2, XBB.1.5.
Vaccine effectiveness (VE) estimates of currently approved vaccines	Relative VE estimates during periods of circulation of XBB, JN.1, KP.3.1.1 or emerging variant(s) * in human populations. Studies need to estimate relative VE by time since vaccination or at least provide a measure of time since vaccination, such as the mean or median. They should also provide variant-specific estimates and distinct estimates for each of the following vaccine antigen compositions across different vaccine platforms: monovalent JN.1, monovalent KP.2, or monovalent XBB.1.5. Studies should also provide relative VE for a range of outcomes beyond severe disease, including any infection or symptomatic disease. Severe disease should not be defined using generic hospital admission data, but rather with specific criteria such as oxygen use, ventilation, or admission to intensive care due to respiratory symptoms.
Data from vaccine manufacturers	Animal and/or human data that demonstrate the breadth and durability in immune responses elicited by vaccines in current portfolio, as well as any vaccine candidates in development, against BA.2, XBB.1.5, JN.1, KP.2, KP.3.1.1 + emerging variants;* Observational epidemiological data that demonstrate the efficacy or effectiveness of any vaccines in current portfolio, as well as any vaccine candidates in development, against BA.2, XBB.1.5, JN.1, KP.2, KP.3.1.1 + emerging variants.*

+ WHO website: https://www.who.int/activities/tracking-SARS-CoV-2-variants

* Key emerging variants that evolve and considered relevant for demonstrating breadth include the list of Variants of Interest (VOI) and Variants Under Monitoring (VUM). This list is maintained on the WHO website: https://www.who.int/activities/tracking-SARS-CoV-2-variants

References

1. World Health Organization. Interim statement on the composition of current COVID-19 vaccines. 17 June 2022. Available from: https://www.who.int/news/item/17-06-2022-interim-statement-on--the-composition-of-current-COVID-19-vaccines.
2. World Health Organization. Statement on the antigen composition of COVID-19 vaccines. 18 May 2023. Available from: https://www.who.int/news/item/18-05-2023-statement-on-the-antigen-composition-of-covid-19-vaccines.
3. World Health Organization. Statement on the antigen composition of COVID-19 vaccines. 13 December 2023. Available from: https://www.who.int/news/item/13-12-2023-statement-on-the-antigen-composition-of-covid-19-vaccines.
4. World Health Organization. Statement on the antigen composition of COVID-19 vaccines. 26 April 2024. Available from: https://www.who.int/news/item/26-04-2024-statement-on-the-antigen-composition-of-covid-19-vaccines.
   

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