Confronting the avian influenza threat: vaccine development for a potential pandemic

Abstract

Sporadic human infection with avian influenza viruses has raised concern that reassortment between human and avian subtypes could generate viruses of pandemic potential. Vaccination is the principal means to combat the impact of influenza. During an influenza pandemic the immune status of the population would differ from that which exists during interpandemic periods. An emerging pandemic virus will create a surge in worldwide vaccine demand and new approaches in immunisation strategies may be needed to ensure optimum protection of unprimed individuals when vaccine antigen may be limited. The manufacture of vaccines from pathogenic avian influenza viruses by traditional methods is not feasible for safety reasons as well as technical issues. Strategies adopted to overcome these issues include the use of reverse genetic systems to generate reassortant strains, the use of baculovirus-expressed haemagglutinin or related non-pathogenic avian influenza strains, and the use of adjuvants to enhance immunogenicity. In clinical trials, conventional surface-antigen influenza virus vaccines produced from avian viruses have proved poorly immunogenic in immunologically naive populations. Adjuvanted or whole-virus preparations may improve immunogenicity and allow sparing of antigen.

Figure 1

Returning from a shopping trip in Hanoi, Vietnam (photo JM Katz).

Figure 2

The effect of highly pathogenic H5N1 virus on ducklings in Vietnam (photo T Tumpey).

Figure 3

Effect of alum-adjuvant on immunogenicity of monovalent influenza A/Singapore/1/57 (H2N2) in immunologically naive people aged 18–30 years (data from reference 71). Vaccine administered on day 0 and day 21. GMT=geometric mean titre. Al=aluminum mineral adjuvant.

Figure 4

Geometric mean titres of antibody for MF59-adjuvanted and conventional surface-antigen H5N3 vaccine before and after two and thre doses of vaccine (data from , A=Haemagglutination-inhibition (H5N3); B=Microneutralisation (H5N3); C=Single radial haemolysis (H5N3); D=single radial haemolysis (H5N1)