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
- 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.
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.
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
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.
