WHO: Candidate Vaccine Viruses for Pandemic Preparedness - Feb 2026 - CDC Update on H5 CVV stockpile

[Michael Coston]

WHO: Candidate Vaccine Viruses for Pandemic Preparedness - Feb 2026




Credit NIAID

#19,070

In addition to deciding which influenza viruses to include in the next seasonal flu vaccine (see WHO Recommendations for Influenza Vaccine Composition for the 2026-2027 Northern Hemisphere Influenza Season), twice each year flu researchers are asked by WHO to advise on the development of new CVVs (Candidate Vaccine Viruses) for zoonotic influenza.

While our attentions are primarily focused on the clade 2.3.4.4b H5N1 virus, there are literally dozens of other zoonotic influenza A viruses circulating around the world (see CDC IRAT list), all of which are believed to have some degree of pandemic potential.

Each year new variants - subclades, subtypes, or genotypes - emerge, and the WHO must decide if they warrant the creation of a CVV. Since H5 viruses evolve rapidly, many older CVVs no longer match circulating strains.

Having a proven CVV already tested and approved can save valuable time if rapid production and distribution of a pandemic vaccine are ever required.

And over the past two decades, the WHO has recommended a lot of them (see list below). Forty-six are approved and available, and 6 are pending. And that's just for H5 subtypes.

They WHO has also approved 22 H7 CVVs (20 available, 2 pending), and 11 H9 CVVs (8 available, 3 pending), along with a smattering of other subtypes (H1, H3, H10, etc.).

This week the WHO published a 13-page update which contains background information on a wide range of novel avian and swine flu viruses detected over the past 6 months.

While they cite ongoing antigenic changes - particularly among the H5Nx panoply of viruses - in the end only one new CVV was recommended for development; a new A/Hunan/40087/2025-like H9N2 CVV.

We've been following concerning antigenic changes in H9N2 viruses for quite some time (see China CDC Weekly: Epidemiological and Genetic Characterization of Three H9N2 Viruses Causing Human Infections — Changsha City, Hunan Province, China, April 2025).

While no new H5 CVVs were recommended, antigenic characterization is still pending on a number of recent human H5 infections, including last September's H5N2 case from Mexico, and several recent H5N1 cases in Cambodia (clade 2.3.2.1e), along with a number of poultry isolates collected from Egypt, Laos, and Brazil.

This report also finds that the recent H5N5 virus isolated from a human in Washington State showed reduced reactivity to existing CVVs.

The HA1 of the A(H5N5) virus from the human case in the United States of America had five amino acid substitutions relative to the A/Astrakhan/3212/2020 CVV, including a gain of a potential glycosylation site. Post-infection ferret antisera raised against clade 2.3.4.4b A/American Wigeon/South Carolina/22-000345-001/2021, A/Ezo red fox/Hokkaido/1/2022 and A/Astrakhan/3212/2020 CVVs showed reduced reactivity to the A(H5N5) virus.

For now, however, the WHO has decided the threshold has not been met to justify recommending the creation of an H5N5 CVV.

I've only posted the summary, follow the link to read it in its entirety. I'll have a bit more after the break.

Genetic and antigenic characteristics of zoonotic influenza A viruses and development of candidate vaccine viruses for pandemic preparedness
February 2026

The development of influenza candidate vaccine viruses (CVVs), coordinated by the World Health Organization(WHO), remains an essential component of the overall global strategy for influenza pandemic preparedness.

Selection and development of CVVs are the first steps towards timely vaccine production and do not imply a recommendation for initiating manufacture. National authorities may consider the use of one or more of these CVVs for pilot lot vaccine production, clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.

Zoonotic influenza viruses continue to be identified and evolve both antigenically and genetically, leading to the need for additional CVVs for pandemic preparedness purposes. Changes in the antigenic and genetic characteristics of these viruses relative to existing CVVs and their potential risks to public health justify the need to develop new CVVs.

This document summarizes the antigenic and genetic characteristics of recent zoonotic influenza viruses and related viruses circulating in animals1 that are relevant to CVV updates. Institutions interested in receiving these CVVs should contact WHO at gisrs@who.int or the institutions listed in announcements published on the WHOwebsite2.

(Continue . . . )


While having a closely-matched CVV might shave weeks or even months off the time it would take to develop, manufacture, and deploy a pandemic vaccine, there are still many obstacles to overcome.

Any flu jab would likely require 2 shots - 30 days apart - and even under the best case scenarios, it would likely take 6 months or longer before substantial quantities of vaccine are available to the public.

Some past blogs on some of the logistics of developing a pandemic vaccine include:

Referral: SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1

NPJ Vaccines: Modeling the Impact of Early Vaccination in an Influenza Pandemic in the United States

How The WHO & CDC Are Developing Candidate H5N1 Vaccines

Manufacturing Pandemic Flu Vaccines: Easier Said Than Done

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https://afludiary.blogspot.com/2026/...ruses-for.html

[Michael Coston]

J.I.D.: Development & Characterization of Candidate Vaccine Viruses against HPAI A(H5) Viruses for Rapid Pandemic Response



WHO H5 CVV list (n=46)

#19,072

Two days ago, in WHO: Candidate Vaccine Viruses for Pandemic Preparedness - Feb 2026, we looked at the latest WHO recommendations for CVVs (Candidate Vaccine Viruses) against zoonotic influenza viruses.

While no new H5 CVVs were recommended, antigenic characterization of several recent isolates were pending, and H5 continues to evolve.

Less well known is that the CDC also maintains their own list of HPAI H5 CVVs - and while there are some overlaps with the WHO's list - there are some differences (see How The WHO & CDC Are Developing Candidate H5N1 Vaccines).

On the same day that the WHO released their semi-annual zoonotic vaccine update recommendations, the Journal of Infectious Diseases published the following CDC review of 25 existing H5 CVVs, and how well they might work against current (U.S & Cambodian) H5N1 strains.

CVVs are `seed viruses' which have been antigenically matched to various legacy strains of H5 - and were determined to grow reasonably well in an egg medium - which means they could be quickly used to begin vaccine manufacturing.

The big caveat is that antigenic matching is done using HI assays in ferrets, which may not fully predict its effectiveness in humans. And - as this report cautions - even tiny changes in the virus can have major impact on its antigenic profile.

In one of their studies, researchers looked at two clade 2.3.2.1e viruses collected from humans in Cambodia in 2023. The two isolates were:

• A/Cambodia/NPH230032/2023
• A/Cambodia/NPH230776/2023

Despite their genetic similarity, they reacted quite differently.

• Encouragingly, the A/Cambodia/NPH230032/2023 virus showed broad cross-reactivity against several legacy CVVs.

• A/Cambodia/NPH230776/2023, however,showed reduced cross-reactivity against many of those same CVVs, with only a specific 2.3.2.1 lineage CVV showing strong inhibition.

While it is possible that an interim vaccine might be developed early in the next pandemic based on an existing CVV - potentially shaving weeks or even months off the manufacturing process - a lot of things would have to go `right'.

But since a targeted strain-specific vaccine could take 6 months or more to develop, having an existing library of CVVs to draw from might save a lot of lives.

I've only posted the abstract, and a few excerpts from the results and discussion. Follow the link to read it in its entirety.

Development and Characterization of Candidate Vaccine Viruses against High Pathogenicity Avian Influenza A(H5) Viruses for Rapid Pandemic Response

Li Wang , Jieru Wang , Jaber Hossain , Hans C Cooper , Cindy Adolphus , Michael Currier , Ginger Atteberry , Chenchen Feng , Marie K Kirby , Han Di ... Show more

The Journal of Infectious Diseases, jiag132, https://doi.org/10.1093/infdis/jiag132
Published: 28 February 2026

PDF

Abstract

High pathogenicity avian influenza A(H5) viruses pose a pandemic threat. These viruses have rapidly evolved in birds and frequently crossed species barriers, resulting in over 1,000 confirmed human infections, with a case fatality proportion of approximately 50%. In response, the U.S. CDC has developed dozens of A(H5) candidate vaccine viruses (CVVs) over the past two decades, primarily targeting clades known to infect humans. This report summarizes the development and characterization of the CVVs, with a particular focus on their antigenic relationships with clades 2.3.2.1e and 2.3.4.4b A(H5N1) viruses, which have been responsible for the majority of recent human infections.

(SNIP)

Given the ongoing A(H5N1) outbreaks in birds and mammals, along with zoonotic transmission to humans caused by clades 2.3.4.4b and 2.3.2.1e, we aimed to evaluate the ability of antibodies raised against these CVVs in ferrets to inhibit hemagglutination of representative strains from these two clades.

Three recent human A(H5) isolates were tested in the HI assay: A/Texas/37/2024(TX37), a clade 2.3.4.4b virus representing the first human case of the 2024 U.S. dairy cattle A(H5)outbreak; A/Cambodia/NPH230776/2023 and A/Cambodia/NPH230032/2023, both clade2.3.2.1e viruses isolated in 2023.

Seven out of 16 heterologous ferret antisera inhibited the TX37 virus with HI titers within a 2-fold difference compared to the homologous HI titer (Table 2). Out of those seven antisera, four were raised against CVVs belonging to genetic clades different from TX37.

Similarly, eight ferret antisera raised against these A(H5) CVVs inhibited A/Cambodia/NPH230032/2023 (2.3.2.1e) despite seven of the CVVs being from heterologous genetic clades. Interestingly, only two ferret antisera inhibited A/Cambodia/NPH230776/2023, though it belongs to clade 2.3.2.1e, the same clade as A/Cambodia/NPH230032/2023 (Table 2).

Twelve amino acid differences within HA1, including substitutions in the receptor-binding domain and antigenic site B, are likely responsible for the observed difference in cross-reactivity of CVV antisera against these two viruses (Supplementary Table 3).
DISCUSSION

In this study, we provided a comprehensive overview of 25 A(H5) CVVs developed at the CDC over the past two decades, including detailed information on their HA titers, EID₅₀ values, and viral protein yields. These CVVs have been distributed to government agencies, vaccine manufacturers, academic institutions, and other stakeholders to facilitate laboratory characterization, regulatory evaluation, and vaccine manufacturing.

(SNIP)

While ferret antisera provide a valuable surrogate model for antigenic characterization, it is important to acknowledge their limitations. Species-specific differences in immune responses between ferrets and humans are well-documented for seasonal influenza viruses [13]. Human serological data for clades 2.3.2.1e and 2.3.4.4b viruses remain limited, although a recent study has begun to address this gap [14]. Future efforts should prioritize evaluating antibody responses in individuals vaccinated with A(H5) vaccines or previously infected with A(H5) viruses to better assess the potential for cross-protection against emerging zoonotic strains.

In conclusion, maintaining a diverse and regularly updated A(H5) CVV library is critical for global readiness as avian influenza viruses continue to evolve. The demonstrated cross-reactivity of several heterologous CVVs with current zoonotic strains underscores the importance of antigenic breadth in CVV selection and suggests that some stockpiled or previously developed candidates may provide adequate protection and enable rapid vaccine production, offering valuable lead time during outbreak response.

(Continue . . .)

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