Vaccination stays an necessary public well being countermeasure towards COVID-19. As per the WHO Director Common’s standing suggestions for COVID-19, Member States are advisable to proceed to supply COVID-19 vaccination primarily based on the suggestions of the WHO Strategic Advisory Group of Specialists on Immunization (SAGE).
SARS-CoV-2 continues to flow into and evolve with necessary genetic and antigenic evolution of the spike protein because the starting of the COVID-19 pandemic. The target of an replace to COVID-19 vaccine antigen composition is to reinforce vaccine-induced immune responses to circulating SARS-CoV-2 variants.
The WHO TAG-CO-VAC advises retaining the usage of a monovalent JN.1 lineage variant because the antigen in future formulations of COVID-19 vaccines. In accordance with WHO SAGE coverage, vaccination shouldn’t be delayed in anticipation of entry to vaccines with an up to date composition; vaccination programmes can proceed to make use of any accessible WHO emergency-use listed or prequalified COVID-19 vaccines.
The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) continues to intently monitor the genetic and antigenic evolution of SARS-CoV-2 variants, immune responses to SARS-CoV-2 an infection and COVID-19 vaccination, and the efficiency of COVID-19 vaccines towards circulating variants. Primarily based on these evaluations, WHO advises vaccine producers and regulatory authorities on the implications for future updates to COVID-19 vaccine antigen composition. In April 2024, the TAG-CO-VAC advisable the usage of a monovalent JN.1 lineage vaccine antigen as one method to induce enhanced neutralizing antibody responses to JN.1 and its descendent lineages. A number of producers (utilizing mRNA and recombinant protein-based vaccine platforms) have up to date COVID-19 vaccine antigen composition to monovalent JN.1 lineage formulations (JN.1 or KP.2) and a few of these have been authorized to be used by regulatory authorities. Earlier statements from the TAG-CO-VAC could be discovered on the WHO web site.
The TAG-CO-VAC reconvened on 10-12 December 2024 to assessment the genetic and antigenic evolution of SARS-CoV-2; immune responses to SARS-CoV-2 an infection and/or COVID-19 vaccination; the efficiency of at the moment authorized vaccines towards circulating SARS-CoV-2 variants; and the implications for COVID-19 vaccine antigen composition.Proof reviewed
The printed and unpublished proof reviewed by the TAG-CO-VAC included: (1) SARS-CoV-2 genetic evolution with further assist from the WHO Technical Advisory Group on SARS-CoV-2 Virus Evolution (TAG-VE); (2) Antigenic characterization of earlier and rising SARS-CoV-2 variants utilizing virus neutralization assessments with animal antisera and additional evaluation of antigenic relationships utilizing antigenic cartography; (3) Immunogenicity information on the breadth of neutralizing antibody responses elicited by at the moment authorized vaccine antigens towards circulating SARS-CoV-2 variants utilizing animal and human sera; (4) Preliminary immunogenicity information on immune responses following an infection with circulating SARS-CoV-2 variants; (5) Accessible vaccine effectiveness (VE) estimates of at the moment authorized vaccines in periods of circulation of XBB.1 and JN.1 lineages; and (6) Preliminary preclinical and scientific immunogenicity information on the efficiency of candidate vaccines with up to date antigens shared confidentially by vaccine producers with TAG-CO-VAC. Additional particulars on the publicly accessible information reviewed by the TAG-CO-VAC could be discovered within the accompanying information annex. Unpublished and/or confidential information reviewed by the TAG-CO-VAC aren’t proven.
Abstract of accessible proof
In 2024, SARS-CoV-2 continues to flow into globally and trigger extreme illness, put up COVID-19 situation and dying. Nearly all of COVID-19 deaths proceed to happen in people aged 65 years and older and people with coexisting situations. There are persistent and growing gaps within the reporting of circumstances, hospitalizations and deaths, from WHO Member States, making epidemiological developments tough to deduce.
Presently circulating SARS-CoV-2 variants are all derived from JN.1. The weekly proportion of XEC sequences amongst all SARS-CoV-2 sequences submitted to GISAID continues to extend, whereas the weekly proportions of all different Variants of Curiosity (JN.1) or Variants Below Monitoring (KP.2, KP.3, KP.3.1.1, JN.1.18 and LB.1) are actually declining. There are different JN.1-derived variants which are at the moment in low proportions, however which have mutations that will give them a bonus over XEC: at the moment LP.8.1, NP.1, LF.7.2 are variants being monitored and/or characterised.
In printed and unpublished information utilizing antisera from naïve animal fashions, circulating JN.1-derived variants (JN.1, JN.1.16.1, KP.2, KP.2.3, KP.3, KP.3.1.1, LB.1 and XEC) are antigenically intently associated.
Evaluation of naïve mice immunized with mRNA vaccine antigens (KP.3, KP.3.1.1, XEC) confirmed that JN.1, KP.3.1.1, XEC are antigenically intently associated to one another (roughly 1 antigenic unit in cartographic evaluation, which corresponds to a two-fold-reduction in neutralization). Antisera to KP.3.1.1 and XEC generate cross-reactive neutralizing antibody titers to one another and to different rising variants.
Antisera from naïve hamsters contaminated with JN.1 descendent lineages confirmed that circulating JN.1-derived variants akin to KP.3.1.1 are antigenically intently associated to JN.1 and to one another (roughly 1 antigenic unit in cartographic evaluation). JN.1 antisera confirmed higher cross-reactivity to KP.2 and KP.3.1.1, as in comparison with KP.2 antisera.
In printed and unpublished information from people, vaccination with monovalent JN.1 or KP.2 antigens considerably elevated neutralizing antibody titers that cross-reacted with all JN.1 descendent lineages examined. Evaluation of pre- and post-vaccination sera from JN.1 or KP.2 immunized people demonstrated that vaccination leads to robust rises in neutralizing antibody titers towards JN.1 and descendent variants, together with KP.2, KP.2.3, KP.3, KP.3.1.1 and XEC. Submit-monovalent JN.1 or KP.2 vaccination neutralizing antibody titers towards KP.3.1.1 and XEC had been modestly decrease (constant 2-fold reductions in titers) than these towards the homologous JN.1 or KP.2 antigens. There have been higher reductions in cross-neutralization of rising JN.1 lineage variants utilizing post-monovalent XBB.1.5 vaccination sera, as in comparison with post-monovalent JN.1 or post-monovalent KP.2 vaccination sera. In a context of infection- and vaccine-derived immunity within the majority of the inhabitants, up to date vaccine effectiveness (VE) estimates are relative (rVE) relatively than absolute (evaluating vaccinated to unvaccinated people). rVE, typically known as “up-to-date VE”, demonstrates the added safety of most up-to-date vaccination over and above pre-existing immunity derived from earlier infections and/or vaccinations. There are at the moment research reporting VE or rVE estimates utilizing monovalent JN.1 lineage (JN.1 or KP.2) vaccines.
Authorised monovalent XBB.1.5 mRNA COVID-19 vaccines continued to supply further safety towards extreme illness and dying in periods of XBB descendent lineage circulation within the first three months after vaccination; rVE level estimates towards symptomatic illness had been usually decrease. In periods of JN.1 descendent lineage circulation, monovalent XBB.1.5 mRNA vaccines continued to indicate further safety within the first three months after vaccination, nevertheless, accessible proof factors in the direction of a discount in rVE estimates towards JN.1-derived variants, as in comparison with XBB.1 lineage variants, for cover towards dying, extreme illness, symptomatic illness and an infection.
The VE estimates for monovalent XBB.1.5 vaccines towards JN.1-derived variants are per reductions in neutralizing antibody titers noticed in preclinical and scientific immunogenicity research of post-monovalent XBB.1.5 vaccination sera towards JN.1 descendent variants, as in comparison with XBB.1 lineage variants.
Preclinical information shared confidentially with the TAG-CO-VAC by vaccine producers present that immunization of naïve mice, in addition to of mice beforehand immunized with SARS-CoV-2 variants with monovalent JN.1-containing or monovalent KP.2-containing vaccine candidates resulted in good neutralization of JN.1 and descendent variants, together with KP.3.1.1, XEC and MC.1. Nonetheless, neutralizing antibody titers towards KP.3.1.1, XEC and MC.1 had been roughly 2-fold decrease than these towards the homologous immunizing antigen. A single preclinical immunogenicity research in mice utilizing an XEC vaccine candidate confirmed comparable neutralizing antibody titers towards JN.1, KP.3.1.1 and XEC as in comparison with a JN.1 vaccine candidate.
Medical information shared confidentially with the TAG-CO-VAC by vaccine producers present that post-monovalent JN.1 sera neutralized JN.1 and its derivatives together with KP.3.1.1 and XEC properly.
The TAG-CO-VAC acknowledges a number of limitations of the accessible information:
There are persistent and growing gaps within the reporting of circumstances, hospitalizations and deaths, from WHO Member States, in addition to in genetic/genomic surveillance of SARS-CoV-2 globally, together with low numbers of samples sequenced and restricted geographic range. The TAG-CO-VAC strongly helps the continuing work of the WHO Coronavirus Community (CoViNet) to handle this data hole.
The timing, particular mutations and antigenic traits of rising and future variants are tough to foretell, and the potential public well being impression of those variants stay unknown. There are JN.1-derived variants akin to LP.8.1, NP.1 and LF.7.2 which are at the moment in low proportions, however which have mutations that will give them extra immune escape than XEC. These will proceed to be monitored and/or characterised. The TAG-CO-VAC strongly helps the continuing work of the TAG-VE.
Though neutralizing antibody titers have been proven to be necessary correlates of safety from SARS-CoV-2 an infection and of estimates of vaccine effectiveness, there are a number of elements of immune safety elicited by an infection and/or vaccination. Knowledge on the immune responses following JN.1 descendent lineage an infection or monovalent JN.1, KP.2 or XBB.1.5 vaccination are largely restricted to neutralizing antibodies. Knowledge and interpretation of different facets of the immune response, together with mobile immunity, are restricted.
Immunogenicity information towards at the moment circulating SARS-CoV-2 variants aren’t accessible for all COVID-19 vaccines. Additional, there are very restricted information on immune responses following an infection in people with current SARS-CoV-2 variants (e.g., KP.3.1.1, XEC).
Estimates of VE towards lately circulating SARS-CoV-2 variants, together with XBB or JN.1 descendent lineages, are restricted by way of the quantity and geographic range of research, vaccine platforms evaluated, populations assessed, and length of follow-up. Moreover, the referent inhabitants for VE estimates varies considerably with respect to prior historical past of vaccination. There are at the moment no direct comparative estimates for monovalent JN.1, KP.2 or XBB.1.5 vaccines versus different antigen composition(s) delivered throughout the identical time interval. Lastly, VE estimates could also be confounded by variations in undocumented infection-derived immunity between teams, resulting in potential underestimation of VE.
Suggestions for COVID-19 vaccine antigen composition
Given the breadth in immune responses demonstrated by monovalent JN.1 lineage vaccines towards circulating variants, the TAG-CO-VAC advises retaining the present COVID-19 vaccine antigen composition, i.e. a monovalent JN.1 lineage variant (NextStrain: 24A, GenBank: PP298019, GISAID: EPI_ISL_18872762) as one method to induce enhanced neutralizing antibody responses to JN.1 and its descendent variants (e.g., KP.3.1.1 and XEC).
Different approaches that show broad and strong neutralizing antibody responses towards at the moment circulating JN.1 descendent lineage variants, akin to vaccine antigens derived from more moderen variants or various formulations, is also thought-about.
As per the WHO Director Common’s standing suggestions for COVID-19, Member States are advisable to proceed to supply COVID-19 vaccination primarily based on the suggestions of the WHO SAGE. Vaccination shouldn’t be delayed in anticipation of entry to vaccines with an up to date composition; vaccination programmes can proceed to make use of any accessible WHO emergency-use listed or prequalified COVID-19 vaccines.Additional information requested
Given the constraints of the proof upon which the suggestions above are derived and the anticipated continued evolution of the virus, the TAG-CO-VAC strongly encourages technology of the next information (along with the kinds of information outlined in October 2024):
Immune responses and scientific endpoints (i.e. VE and/or comparator charges of an infection and extreme illness) in diversified human populations who obtain COVID-19 vaccines with a monovalent JN.1 or KP.2 vaccine antigen composition, throughout completely different vaccine platforms, in addition to additional scientific and laboratory information on the efficiency of all at the moment authorized COVID-19 vaccines towards rising SARS-CoV-2 variants.
Strengthened epidemiological and virological surveillance, as per the Standing Suggestions for COVID-19 in accordance with the Worldwide Well being Rules (2005), to find out if rising variants are antigenically distinct and capable of displace circulating variants.
Medical analysis of related new vaccine antigens derived from more moderen variants.
As beforehand said, the TAG-CO-VAC continues to encourage the additional growth of vaccines that will enhance safety towards an infection and cut back transmission of SARS-CoV-2.
The TAG-CO-VAC will proceed to intently monitor the genetic and antigenic evolution of SARS-CoV-2 variants, immune responses to SARS-CoV-2 an infection and COVID-19 vaccination, and the efficiency of COVID-19 vaccines towards circulating variants. The TAG-CO-VAC may also proceed to reconvene each six months to guage the implications for COVID-19 vaccine antigen composition. At every assembly, suggestions to both preserve present vaccine composition or to contemplate updates shall be issued.
