by Prof. H. Fleury, MD, PhD, University of Bordeaux and Ventum Biotech
Human influenza viruses are antigenically classified into A, B and C.
A and B are regularly associated with epidemics in humans.
B is relatively stable genomically, and epidemics are linked to drift (changes in a few amino acids) in the surface proteins H (hemagglutinin) and N (neuraminidase), those that are recognized in the first line by the human immune system, including neutralizing antibodies.
Influenza A has a great antigenic variability because it is present in humans and in animals, especially birds. Wild aquatic birds are the ancestral reservoir of influenza A viruses; they carry different viruses and transmit them to domestic birds and mammals. While a limited number of surface antigens are known in human influenza viruses (H1N1, H2N2, H3N2), the variability of H and N is much greater in birds and includes, among others, H5N1, H3N8, H7N7, H9N2, H7N2, H7N3, H7N9, H10N7, etc.
Humans can be affected by two phenomena:
A reassortment between a human virus and an avian virus, possibly in an intermediate host such as pigs: this is how the 1968 Hong Kong flu arose, from a reassortment between a human H2N2 virus and a duck strain carrying H3, the human virus acquiring the gene coding for H3.
Direct contamination by an avian virus, a rare event once thought to be impossible, first documented in severe cases in 1997 in Hong Kong, when humans were directly infected with an H5N1 virus from chickens.
The H5N1 virus is particularly interesting because it migrated via wild birds from Asia to Africa and Europe and then to North and South America with a highly pathogenic variant (HPAI: highly pathogenic avian influenza) for the birds themselves (marine or farmed).
In the Americas it infected mammals: seals, felines (including cats), dairy cows... (and mink farms in Europe).
Human infection is rare, but historically about half of reported cases have been fatal; most recent US cases, mainly in farm workers, have been mild.
The question that arises is therefore whether avian H5N1 will reassort with a human H3N2 virus to give rise to an H5N2 virus, for example. Or whether the H5N1 virus will present one or more mutation(s) of adaptation to transmission to humans, thus leading to an epidemic or even a pandemic?
With the increase in H5N1 infections in the USA in cows and other mammals (cats, for example) in contact with humans, the question of a pandemic emergence is raised.
While H5N1 holds pole position for a human pandemic, other avian candidates have been described, such as H5N6, H7N9 and H9N2.
The fight against a possible avian pandemic will involve the synthesis of vaccines directed against H5N1 or even against several avian strains and the use of antiviral molecules directed against neuraminidase (N) or against replication enzymes.
Confirmed human cases of avian influenza A(H5N1) reported to WHO, by country (cumulative, November 2003 - November 2026)
Australia 1
Azerbaijan 8
Bangladesh 15
Cambodia 96
Canada 2
Chile 1
China 57
Djibouti 1
Ecuador 1
Egypt 359
India 4
Indonesia 200
Iraq 3
Lao People’s Democratic Republic 3
Mexico 1
Myanmar 1
Nepal 1
Nigeria 1
Pakistan 3
Spain 2
Thailand 25
Turkey 12
United Kingdom 6
United States 72
Vietnam 130
Overall 1005
Source: WHO data, compiled by the Hong Kong Centre for Health Protection (Avian Influenza Report, week 44, 2026)
