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Vaccine. 2008 Apr 16;26(17):2062-72. doi: 10.1016/j.vaccine.2008.02.047. Epub 2008 Mar 13.

Comparison of vaccines for induction of heterosubtypic immunity to influenza A virus: cold-adapted vaccine versus DNA prime-adenovirus boost strategies.

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Center for Biologics Evaluation and Research, Food and Drug Administration , Rockville, MD 20852-1448, USA.


Influenza epidemics or pandemics can arise for which strain- or subtype-matched vaccines are unavailable. Heterosubtypic immunity (Het-I) targeting conserved influenza A antigens could reduce morbidity and mortality during preparation of matched vaccines. Various vaccines inducing Het-I in animals have been studied separately using different viruses and conditions, but effectiveness for inducing Het-I has not been directly compared. The present studies compared immunization with cold-adapted (ca) viruses to DNA prime-recombinant adenovirus (rAd) boost vaccination to conserved antigens nucleoprotein (NP), matrix-2 (M2), or A/NP+M2. Both ca and DNA-rAd vaccinations induced antibody and T cell responses, and protected against lethal H1N1 challenge. Only A/NP+M2 DNA-rAd protected against challenge with highly pathogenic A/Vietnam/1203/2004 (H5N1); ca vaccine did not. Existing ca vaccines may provide some Het-I, but experimental vaccination focusing on conserved antigens was more effective in this model for protection against a divergent, highly pathogenic virus.

[Indexed for MEDLINE]

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