#18,785
While the WHO, CDC, ECDC, and other public health agencies continue to assess the risk to the general public from the H5Nx influenza virus as LOW, these viruses continue to evolve, spread, and make inroads into new hosts (including humans).
As concerns mount, countries around the world have begun to purchase varying amounts of pre-pandemic H5 vaccines for their populations.- The United States ordered about 4.8 million doses last summer, enough for about 2.4 million people.
- While last December the UK announced plans to purchase 5 million doses.
- Six Months ago Canada announced plans to Purchase 500,000 doses Of H5N1 Vaccine
- And last April the EU announced plans to purchase up to 27 million doses.
Last February, Canada's NACI released preliminary guidance that considers when - and to whom - it might be appropriate to deploy an H5N1 vaccine during a pre-pandemic time period.
It is not as straightforward as one might think, as vaccination for a novel flu strain generally requires two doses - 30 days apart - so these purchases would only serve as a stop-gap measure for a relatively small number of high risk individuals (e.g. laboratory personnel conducting H5 testing, those working with infected animals, healthcare workers, etc.).
Additional doses could take many months to manufacture in any useful quantity, and no one really knows how effective any of these pre-existing vaccines would be against an emerging H5Nx virus (see Maggie Fox's SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1).
All of which brings us to a 46-page WHO guidance document - based, in large part, on a September 2024 WHO virtual scientific consultation - on:
OverviewWHO conducted a virtual scientific expert consultation on A(H5) vaccines and vaccination. This report provides an overview of the landscape of A(H5) vaccines and summarizes options for Member States' potential use of A(H5) vaccination during the interpandemic and emergence periods.
WHO Team
Global Influenza Programme (GIP), i-MCM-Net, PIP Framework, Preparedness and Resilience for Emerging Threats (PRET)
EXECUTIVE SUMMARYAvian influenza viruses – particularly A(H5) – pose a significant risk for potential pandemics as they can infect humans and other mammals. The high mutation rate of influenza viruses raises concerns about their potential to adapt for efficient human-to-human transmission. Influenza vaccines are crucial tools in mitigating the impact of influenza epidemics and pandemics.Given the global circulation of A(H5) viruses – especially the spillover to dairy cattle since early 2024 – and the rapidly evolving vaccine landscape, the World Health Organization (WHO) held a virtual scientific consultation on 12–13 September 2024 to review the current global A(H5) epidemiological situation; the availability and landscape of A(H5) vaccines and their characteristics; updated evidence on A(H5) vaccine immunogenicity, safety and other characteristics; and considerations for the use of A(H5) vaccines, based on expert opinions.
The consultation did not discuss A(H5) vaccine stockpiles; A(H5) vaccine regulatory approvals or access issues; mathematical modelling to inform options for use of A(H5) vaccines in the context of other public health measures and stockpiles; acceptance, cost, cost–effectiveness, risk–benefit ratios or other programmatic considerations; or strategies for animal A(H5) vaccination.Topics such as equity were also not discussed, as the Pandemic Influenza Preparedness Framework has enabled WHO to make significant progress in preparing for equitable access to vaccines.The primary objective of the virtual scientific consultation was to update WHO’s Options for the use of human H5N1 influenza vaccines and the WHO H5N1 vaccine stockpile, which was developed during a previous scientific consultation on A(H5N1) held in October 2007. The participants in the 2024 consultation included experts from research academia, WHO collaborating centres and essential regulatory laboratories of the Global Influenza Surveillance and Response System, experts from countries, the WHO Strategic Advisory Group of Experts (SAGE) Secretariat, industry associations and other partners.
This report summarizes the outcomes of the virtual scientific consultation, and is expected to be used during the potential update of SAGE recommendations on the use of licensed H5N1 vaccines. The A(H5) vaccine landscape included in this report is up to date as of 31 March 2025.A(H5) viruses pose a threat to human and animal health globally. National, regional and global preparedness is needed urgently. Countries should remain vigilant in conducting surveillance for emerging influenza viruses with pandemic potential. WHO will continue to monitor the situation and provide updated risk assessments, guidance and technical support, where needed.
This report covers a lot of ground, and really deserves to be read in its entirety. I've lifted a few excerpts below for your perusal.
Safety: summary of the evidence
Influenza vaccines are one of the primary pharmaceutical interventions against influenza. While the safety of seasonal influenza vaccines is well established, A(H5) influenza vaccines have not been widely used in human populations outside clinical evaluation studies.
Based on currently available evidence, all the vaccines licensed have undergone and passed clinical trials for safety. Among the at least 32 000 individuals who received a currently approved A(H5) vaccine in a clinical trial, no major safety concerns have been reported.
Safety data are more limited for specific populations such as children, pregnant or lactating individuals and individuals with underlying health conditions.
(SNIP)
Immunogenicity: summary of the evidence
Data on A(H5) vaccine efficacy or effectiveness in humans are not available. Current vaccines are evaluated and licensed based on immunogenicity measures that are expected to confer protection against A(H5) influenza virus.
A(H5) influenza vaccines are immunogenic, although variability in the level of immunogenicity between vaccines is great. Seroprotection or seroconversion rates based on A(H5) antibody responses range between 44% and 100% for current vaccines, with considerable variability between vaccines and across age groups (see Annex 1).In general, immunogenicity tends to be lower in older adults. Adjuvanted vaccines – particularly those using MF59 and AS03 – are more immunogenic than unadjuvanted vaccines. Product-by-product comparisons are difficult, as vaccines are often clinically evaluated individually in studies, and different assays or immunogenicity end-points are used across studies.
Immune responses to A(H5) vaccines have typically been lower than those to seasonal influenza vaccines, requiring significantly greater antigen amount and two doses or a squalene-based adjuvant for an adequate response.
(SNIP)
Cross-reactivity: summary of the evidence
As part of pandemic preparedness, WHO, through GISRS, regularly updates and makes available candidate vaccine viruses of different influenza subtypes including A(H5) (71). In view of the epidemiological situation of A(H5) influenza, some vaccine manufacturers have initiated production of an A(H5) vaccine using currently available candidate vaccine viruses.
Current A(H5) vaccines demonstrate varying cross-reactive immune responses to antigenically distinct viruses from different clades or sub-clades. Different A(H5) viruses are responsible for human infections worldwide. These differ antigenically at the clade, sub-clade and virus level. It is anticipated that further evolution and divergence will occur among these viruses. Increasing availability of A(H5) vaccines capable of inducing cross-reactive and cross-protective immunity against both currently circulating and future emerging strains would be highly beneficial.
Studies indicate that many of the current A(H5) vaccines demonstrate some degree of cross-reactivity to viruses representing different clades or sub-clades (72). This is primarily found in oil-in-water adjuvanted A(H5) IIVs, although it has also been reported in aluminium-adjuvanted A(H5) IIVs and unadjuvanted A(H5) LAIVs. Cross-reactivity may include multiple cross-clade or sub-clade responses.
(SNIP)
Degree of protection and duration of immune responses: summary of the evidence
The primary outcome desired from A(H5) vaccination is the prevention of severe disease, including hospitalization and death due to A(H5) infection in vaccinated individuals. Based on immunogenicity data, current vaccines are expected to provide some degree of protection against severe disease caused by human infection with related A(H5) viruses for up to six months following vaccination.
In animal models, current evidence indicates that some human A(H5) influenza vaccines can confer protection against disease from homologous and heterologous viruses. No corresponding protection data are available from human studies.
Evidence on the durability of immune responses following vaccination with current A(H5) vaccines is limited. Several vaccines have shown persistence of antibodies at least six months after vaccination, though levels decrease significantly from peak over this period, and vary between vaccines. Data beyond 12 months are very limited, and available data on the duration of immune responses mostly focus on serum antibody levels. It is possible that memory B and T cells may activate strongly on exposure to A(H5) virus and stimulate production of high antibody titres.
The report then delves into how and when vaccines might be deployed. Among the considerations listed, they highlight:
• Vaccine effectiveness: Vaccines are not 100% effective in preventing infection and effectiveness may change over time.
• Vaccine schedule: Currently licensed A(H5) vaccine products require two doses with several weeks between the first and second doses; the optimal interval between doses is not well understood.16
• Risk communication and community engagement: Strong, two-way risk communication and community engagement are needed to respond to mis- and disinformation and to support vaccine uptake.
• Acceptability: A(H5) vaccine acceptance may depend largely on the context in which it is used (for example, outbreaks in animals, zoonotic infections and the severity of human infection) and the associated perception of benefit. The accepted level of risk of adverse events may increase as disease levels rise – particularly if disease is associated with serious morbidity or mortality.
• Landscape of next-generation vaccine products: As the landscape of next-generation influenza vaccine products evolves, universal influenza vaccines and/or next-generation vaccines that induce broad cross-reactivity against many influenza subtypes may become available. While these are still only in the developmental pipeline (and not expected to become available in the near future), they have the potential to change the landscape and options for A(H5) vaccination considerably (78,79).
The upshot, at least in the opening months of any flu pandemic, is that there will only be limited quantities of vaccine available, and their effectiveness won't be known until months into the outbreak.
Which means - unpopular as they might be - NPIs (non-pharmaceutical interventions like masks, social distancing, etc.) will once again become our first line of defense.We've also seen cautionary reports (see St. Jude Researchers: Current Antivirals Likely Less Effective Against Severe Infection Caused by Bird Flu in Cows’ Milk), suggesting our antiviral armamentarium may be inadequate for dealing with an H5 pandemic.
Assuming, of course, enough people have the foresight to stockpile masks and respirators before the next crisis emerges.Not ideal, obviously. But they proved their worth during the last pandemic, and will likely do so again.
