The highly pathogenic H5N1 avian influenza virus (clade 2.3.4.4b) has severely threatened U.S. farms. The virus has been detected in 13 states, including Texas and North Carolina, where it has spread among dairy herds and other animals. Eight cases of human infection have been reported, mostly among farm workers who had contact with infected cows and poultry. Fortunately, symptoms in infected individuals were mild; however, the virus still poses a significant public health risk.
Detecting viral RNA in dairy products has raised concerns over food safety, prompting the U.S. Food and Drug Administration (FDA) and the U.S. Department of Agriculture (USDA) to issue stringent quality control guidelines for milk.
H5N8: A Potential Foundation for an H5N1 Vaccine
In December 2020, the avian influenza A H5N8 virus (clade 2.3.4.4b) was isolated from nasopharyngeal swabs of poultry farm workers during an outbreak at a poultry facility in the Astrakhan region, Russia. The currently circulating H5N1 virus is highly similar to the previous H5N8 strain, differing by only four amino acids. Therefore, the H5N8 virus (A/Astrakhan/3212/2020) is a potential basis for developing a vaccine against the new H5N1 strain.
One vaccine candidate based on the H5N8 strain has shown cross-reactivity with the H5N1 virus. This means the immune system, which produces antibodies against H5N8, can recognize and respond to H5N1 due to the virus’s antigenic similarity. Studies in ferrets confirmed that serum from H5N8-infected animals could effectively combat the new H5N1 influenza virus.
Clinical trials are underway for two versions of the H5N1 vaccine: one based on cell-cultured antigen with an MF59 adjuvant and another using egg-derived antigen with an AS03 adjuvant to enhance immune response.
Early H5N1 Vaccines Provide Protection Against H5N8
The U.S. national stockpile contains three licensed H5N1 influenza vaccines (clades 1 and 2.1) from the early 2000s, prepared for potential pandemic deployment. Scientists evaluated whether these vaccines could neutralize the H5N8 clade 2.3.4.4b virus to help prevent the spread of the emerging H5N1 virus among humans.
The H5N1 influenza vaccines under investigation, derived from HPAI H5N1 strains circulating in Vietnam and Indonesia, include:
- Sanofi Pasteur – non-adjuvanted,
- Seqirus – with or without MF59 adjuvant,
- GSK – with or without AS03 adjuvant.
Study participants included 66 adults vaccinated during clinical trials. Before vaccination, no cross-neutralizing antibodies against H5N1 and H5N8 were detected. After vaccination, participants exhibited varying levels of immune response:
- Participants who received two doses of the Sanofi Pasteur non-adjuvanted vaccine had moderate levels of binding antibodies, low levels of hemagglutination-inhibiting (HAI) antibodies, and moderate levels of neutralizing antibodies against the vaccine H5N1 Vietnam strain. However, cross-reactivity with the H5N8 strain was reduced: binding antibodies decreased fivefold, and HAI antibodies threefold. While neutralizing antibody levels against H5N8 were comparable to those against the vaccine strain, only 58% of participants developed them.
- Participants who received three doses of the Seqirus non-adjuvanted vaccine at 15 µg displayed low binding and neutralizing antibodies against the vaccine strain.
- Participants who received two doses of the Seqirus MF59-adjuvanted vaccine exhibited higher levels of binding antibodies, and neutralizing antibodies were observed in 75% of cases. After a third dose, binding and neutralizing antibody levels increased 2.5-fold, with a 100% seroconversion rate in virus neutralization tests. Additionally, three doses induced cross-reactive antibodies against the H5N8 strain. Ninety-five percent of participants produced high levels of H5N8-neutralizing antibodies.
- The GSK non-adjuvanted vaccine-induced neutralizing antibodies in only one out of eight participants for both the vaccine strain and H5N8. However, participants receiving two doses of this vaccine exhibited high binding antibodies for the strain. HAI antibodies were developed in 86% of participants, while neutralizing antibodies were present.
Two doses of the GSK AS03-adjuvanted vaccine induced cross-reactivity with the H5N8 strain. Approximately 64% of participants developed HAI antibodies, and 77% produced neutralizing antibodies at low to moderate levels.
Conclusion
MF59- and AS03-adjuvanted vaccines generate cross-neutralizing antibodies against H5N8, a candidate strain for a vaccine targeting the circulating H5N1 virus, which has caused outbreaks in U.S. poultry and dairy cattle and holds zoonotic potential.
These findings warrant further validation in larger groups, and neutralization titers should be compared to those from adults vaccinated with H5 clade 2.3.4.4b influenza, which is currently undergoing clinical evaluation.
Useful article, necessary information? Share it!
Someone will also find it useful and necessary:
