Abstract
Achieving broad-spectrum immunity against emerging zoonotic viruses such as avian influenza H5N1 and other possible pandemic viruses will require generation of cross-protective immune responses. Strong antibody responses generated against the H5HA protein are protective, however, antigenic variation between diverging isolates can interfere with virus neutralization. The current study investigates co-administration of an H5 HA DNA vaccine with other variable and conserved influenza antigens (NA, NP, and M2). All antigens were derived from the A/Hanoi/30408/2005 (H5N1) virus and the contribution towards overall protection and immune activation was assessed against lethal homologous and heterologous challenges. An (HA. +. NA) combination afforded the best protection against homologous challenge and (HA. +. NP) was comparable to HA alone against heterologous A/Hong Kong/483/1997 challenge. Interestingly, combining all four H5 antigens at a single site did not improve protection against matched challenge and unexpectedly reduced survival by 30% against a heterologous challenge. Survival was also significantly decreased against heterologous challenge following combination of (HA. +. NP) with an unrelated antigen. Although there were no significant changes in antibody titres, significantly lower T-cell responses were detected against all antigens except HA in each combination. Co-administration of the vaccines at different injection sites restored T-cell responses but did not improve overall protection. Similar observations were also recorded following combination of HA and NP antigens using two different adenovirus-based backbones. Overall, the data suggest that co-administering certain H5N1 antigens offer better or comparable protection to HA alone, however, combining extra antigens may be unnecessary and lead to unfavourable immune responses.
Original language | English (US) |
---|---|
Pages (from-to) | 626-636 |
Number of pages | 11 |
Journal | Vaccine |
Volume | 30 |
Issue number | 3 |
DOIs | |
State | Published - Jan 11 2012 |
Externally published | Yes |
Keywords
- Antibody response
- Antigen combination
- Antigen competition
- Cell-mediated response
- DNA vaccine
- H5N1 influenza
- Multivalent vaccine
ASJC Scopus subject areas
- Molecular Medicine
- General Immunology and Microbiology
- General Veterinary
- Public Health, Environmental and Occupational Health
- Infectious Diseases