Statement on the antigen composition of COVID-19 vaccines

18 December 2025
Statement
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Key points:

  • The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) held its twice-yearly decision-making meeting in December 2025 to review the evolution of SARS-CoV-2, the performance of currently approved COVID-19 vaccines and the implications for COVID-19 vaccine antigen composition.
  • The objective of an update to COVID-19 vaccine antigen composition is to enhance vaccine-induced immune responses to circulating SARS-CoV-2 variants.
  • Following this meeting, the TAG-CO-VAC advises vaccine manufacturers that monovalent LP.8.1 is the recommended vaccine antigen.
  • The previously recommended JN.1 lineage (JN.1 or KP.2) antigens remain suitable alternatives and vaccination should not be delayed in anticipation of access to vaccines with the LP.8.1 composition.
  • Other approaches that demonstrate broad and robust neutralizing antibody responses or efficacy against currently circulating SARS-CoV-2 variants could also be considered.
  • Vaccination remains an important public health countermeasure against COVID-19. As per the WHO Director General’s standing recommendations for COVID-19, Member States are recommended to continue to offer COVID-19 vaccination based on the recommendations of the WHO Strategic Advisory Group of Experts on Immunization (SAGE).

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. In May 2025, the TAG-CO-VAC recommended that monovalent JN.1 or KP.2 remain appropriate vaccine antigens and that monovalent LP.8.1 is a suitable alternative vaccine antigen. Multiple manufacturers (using mRNA or recombinant protein-based vaccines) have updated COVID-19 vaccine antigen composition to monovalent JN.1 lineage formulations (JN.1, KP.2 or LP.8.1). Several of these vaccines have been approved for use by regulatory authorities and have been introduced into vaccination programmes. Previous statements from the TAG-CO-VAC can be found on the WHO website.

The TAG-CO-VAC reconvened on 8-9 December 2025 to review the genetic and antigenic evolution of SARS-CoV-2; immune responses to SARS-CoV-2 infection and/or COVID-19 vaccination; the performance of currently approved vaccines against circulating SARS-CoV-2 variants; and the implications for COVID-19 vaccine antigen composition.

Evidence reviewed

The published and unpublished evidence reviewed by the TAG-CO-VAC included: (1) SARS-CoV-2 genetic evolution with additional support from the WHO Technical Advisory Group on Virus Evolution (TAG-VE); (2) Antigenic characterization of previous and emerging SARS-CoV-2 variants using virus neutralization tests with animal antisera and further analysis of antigenic relationships using antigenic cartography; (3) Immunogenicity data on the breadth of neutralizing antibody responses elicited by currently approved vaccine antigens against circulating SARS-CoV-2 variants using animal and human sera; (4) Preliminary clinical immunogenicity data on immune responses following infection with circulating SARS-CoV-2 variants; (5) Available relative vaccine effectiveness (VE) estimates of currently approved vaccines during periods of JN.1 lineage circulation; and (6) Preliminary non-clinical and clinical immunogenicity data on the performance of candidate vaccines with updated antigens shared confidentially by vaccine manufacturers with TAG-CO-VAC. Further details on the data reviewed by the TAG-CO-VAC can be found in the accompanying data annex. Confidential data reviewed by the TAG-CO-VAC are not shown.

Summary of available evidence

  • There are persistent and increasing gaps in the reporting of cases, hospitalizations and deaths, from WHO Member States, limiting the interpretation of epidemiological trends. Nonetheless, in 2025, SARS-CoV-2 continues to circulate globally, causing severe disease, post COVID-19 condition, and death. Globally, the majority of COVID-19 deaths continue to occur in individuals aged 65 years and older and those with underlying comorbidities.
  • As of early December 2025, most circulating SARS-CoV-2 variants worldwide remain derived from JN.1. In most regions, SARS-CoV-2 Variant Under Monitoring (VUM) XFG is the predominant variant among SARS-CoV-2 sequences submitted to GISAID, typically accounting for 70-80% of all variants reported. In contrast, in several countries in the WHO Western Pacific Region in which SARS-CoV-2 sequencing continues, VUM NB.1.8.1 has been the most recent predominant variant, with XFG detected at lower levels. VUM BA.3.2, first detected in November 2024, continues to be detected at low levels globally; however, higher levels have been reported in limited geographic areas, particularly in wastewater and clinical samples in Western Australia. The proportions of JN.1 (Variant of Interest) and all other VUMs (KP.3.1.1 and LP.8.1) are declining and are now detected at low levels.
  • Published and unpublished neutralization data using antisera from naïve mice and hamsters infected with JN.1 or XFG, as well as mice immunized with mRNA vaccine antigens JN.1, LP.1.8.1, NB.1.8.1 or XFG, indicate that recent JN.1-derived variants are antigenically closely related. These variants differ by approximately 1 antigenic unit in cartographic analyses, corresponding to a two-fold-difference in neutralization, with XFG often the most antigenically distant from JN.1 within the JN.1 cluster. In contrast, these antisera showed limited neutralization activity against BA.3.2, indicating that BA.3.2 is antigenically distinct from circulating JN.1-derived variants.
  • Sera collected in 2025 from individuals with prior SARS-CoV-2 infection or COVID-19 vaccination showed a moderate reduction in neutralizing antibody titers against BA.3.2, as compared to those against JN.1 and LP.8.1.
  • Published and unpublished human serological data of pre- and post-vaccination sera from individuals immunized with JN.1 or KP.2 demonstrated significant increases in neutralizing activity against JN.1 and its descendent lineages. Post-vaccination neutralizing antibody titers against NB.1.8.1 and XFG were lower than those against the homologous JN.1 or KP.2 antigens, with even larger reductions observed for BA.3.2.
  • Pre- and post-vaccination sera from individuals immunized with LP.8.1 demonstrated significant increases in neutralizing activity against JN.1 and its descendent lineages, including NB.1.8.1 and XFG. Post-vaccination neutralizing antibody titers against BA.3.2 were lower than against the homologous LP.8.1 antigen and other JN.1-derived variants.
  • Contemporary vaccine effectiveness (VE) estimates are relative (rVE), rather than absolute (comparing vaccinated to unvaccinated individuals), and demonstrate the added or incremental protection of recent vaccination over and above pre-existing infection- and vaccine-derived immunity. Monovalent JN.1 and KP.2 mRNA vaccines demonstrated additional protection—relative to pre-existing immunity—against symptomatic and severe COVID-19. There are currently no studies reporting VE or rVE estimates using monovalent LP.8.1 vaccines.
  • Data shared confidentially with the TAG-CO-VAC by vaccine manufacturers showed that:
    • Immunization of naïve mice and mice previously immunized with SARS-CoV-2 variants with monovalent JN.1 elicited high neutralizing antibody titers against JN.1, XEC, LP.8.1, NB.1.8.1. Neutralization titers against XFG were typically lower than those against the homologous immunizing antigen, with further reductions observed against BA.3.2.
    • Immunization of naïve mice and mice previously immunized with SARS-CoV-2 variants with monovalent LP.8.1 induced high neutralizing antibody titers against the homologous antigen, JN.1, NB.1.8.1 and XFG. Reductions in antibody titers were consistently observed against BA.3.2.
    • In humans, vaccination with monovalent JN.1 elicited robust neutralizing antibody responses against JN.1, XEC, LP.8.1 and NB.1.8.1. As observed in mice, post-monovalent JN.1 vaccination neutralizing antibody titers against XFG and BA.3.2 were lower than those against the homologous JN.1 antigen. Vaccination with 8.1 induced strong increases in neutralizing antibody titers against JN.1, LP.8.1, NB.1.8.1 and XFG. As in mice, post-monovalent LP.8.1 vaccination neutralizing antibody titers against BA.3.2 were lower than those against the homologous LP.8.1 antigen.

Overall, LP.8.1 as a vaccine antigen offers modestly but significantly increased cross-reactive antibody responses to currently circulating JN.1-derived variants, as compared to monovalent JN.1 or KP.2 vaccines.

The TAG-CO-VAC acknowledges several limitations of available data: 

  • There are persistent and increasing gaps in the reporting of cases, hospitalizations and deaths, from WHO Member States, as well as in genetic/genomic surveillance of SARS-CoV-2 globally, including low numbers of samples sequenced and limited geographic diversity. The TAG-CO-VAC strongly supports the ongoing work of the WHO Coronavirus Network (CoViNet) and the Global Influenza Surveillance and Response System (GISRS) to address this information gap.
  • The timing, specific mutations and antigenic characteristics of emerging and future variants are difficult to predict, and the potential public health impact of these variants remain unknown. While most circulating variants are currently derived from JN.1, there are long branch saltation variants, such as BA.3.2, that are currently detected in low proportions of SARS-CoV-2 variants sequenced globally. Available data indicate that BA.3.2 does not currently exhibit a clear fitness advantage over JN.1-derived variants; however, its future evolutionary potential remains uncertain. These variants will continue to be monitored and/or characterized and the TAG-CO-VAC strongly supports the ongoing work of the TAG-VE. 
  • Although neutralizing antibody titers have been shown to be important correlates of protection from SARS-CoV-2 infection and of estimates of vaccine effectiveness, there are multiple components of immune protection elicited by infection and/or vaccination. Data on the immune responses following JN.1 descendent lineage infection or monovalent JN.1, KP.2 or LP.8.1 vaccination are largely restricted to neutralizing antibodies. Data and interpretation of other aspects of the immune response, including cellular immunity, are limited. 
  • Immunogenicity data against currently circulating SARS-CoV-2 variants are not available for all COVID-19 vaccines. 
  • Estimates of rVE against recently circulating JN.1 variants are limited in terms of the number of studies, geographic diversity, vaccine platforms evaluated, populations assessed, duration of follow-up, and contemporary comparisons of vaccines with different antigen composition.

Recommendations for COVID-19 vaccine antigen composition

Monovalent LP.8.1 (NextStrain: 25A; GenBank: PV074550.1; GISAID: EPI_ISL_19467828) is the recommended COVID-19 vaccine antigen.

As vaccination should not be delayed in anticipation of access to vaccines with an LP.8.1 composition, previously recommended JN.1 lineage (JN.1 or KP.2) antigens remain suitable alternatives.

Other approaches that demonstrate broad and robust neutralizing antibody responses or efficacy against currently circulating SARS-CoV-2 variants could also be considered.

As per the WHO Director General’s standing recommendations for COVID-19, Member States are recommended to continue to offer COVID-19 vaccination based on the recommendations of the WHO SAGE.

Further data requested

Given the limitations of the evidence upon which the recommendations above are derived and the anticipated continued evolution of the virus, the TAG-CO-VAC strongly encourages generation of the following data (in addition to the types of data outlined in September 2025): 

  • Immune responses and clinical endpoints (i.e. VE and/or comparator rates of infection and severe disease) in varied human populations who receive currently approved COVID-19 vaccines against emerging SARS-CoV-2 variants, across different vaccine platforms.
  • Strengthened epidemiological and virological surveillance, as per the Standing Recommendations for COVID-19 in accordance with the International Health Regulations (2005), to determine if emerging variants are antigenically distinct and able to displace circulating variants.
  • Strengthened epidemiological surveillance to characterize disease severity in immunologically naïve and/ or immature individuals (i.e. birth cohorts).
  • Non-clinical and clinical immunogenicity data against circulating SARS-CoV-2 variants for vaccine candidates with different SARS-CoV-2 antigens, such as BA.3.2.

As previously stated, the TAG-CO-VAC continues to encourage the further development of vaccines that may improve protection against infection and reduce transmission of SARS-CoV-2.

The TAG-CO-VAC will continue 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. The TAG-CO-VAC will also continue to reconvene every six months, or as needed, to evaluate the implications for COVID-19 vaccine antigen composition. At each meeting, recommendations to either maintain current vaccine composition or to consider updates will be issued. Prior to each meeting, the TAG-CO-VAC will publish an update to the statement on the types of data requested to inform COVID-19 vaccine antigen composition deliberations.