tetano
Editor, Senior Moderator
Sci Transl Med 15 August 2012:
Vol. 4, Issue 147, p. 147ra114
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3004273
Research Article
Influenza
Elicitation of Broadly Neutralizing Influenza Antibodies in Animals with Previous Influenza Exposure
Chih-Jen Wei1,
Hadi M. Yassine1,
Patrick M. McTamney1,
Jason G. D. Gall2,
James R. R. Whittle1,
Jeffrey C. Boyington1 and
Gary J. Nabel1,*
+ Author Affiliations
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892?3005, USA.
2GenVec Inc., Gaithersburg, MD 20878, USA.
↵*To whom correspondence should be addressed. E-mail: gnabel@nih.gov
Abstract
The immune system responds to influenza infection by producing neutralizing antibodies to the viral surface protein, hemagglutinin (HA), which regularly changes its antigenic structure. Antibodies that target the highly conserved stem region of HA neutralize diverse influenza viruses and can be elicited through vaccination in animals and humans. Efforts to develop universal influenza vaccines have focused on strategies to elicit such antibodies; however, the concern has been raised that previous influenza immunity may abrogate the induction of such broadly protective antibodies. We show here that prime-boost immunization can induce broadly neutralizing antibody responses in influenza-immune mice and ferrets that were previously infected or vaccinated. HA stem?directed antibodies were elicited in mice primed with a DNA vaccine and boosted with inactivated vaccine from H1N1 A/New Caledonia/20/1999 (1999 NC) HA regardless of preexposure. Similarly, gene-based vaccination with replication-defective adenovirus 28 (rAd28) and 5 (rAd5) vectors encoding 1999 NC HA elicited stem-directed neutralizing antibodies and conferred protection against unmatched 1934 and 2007 H1N1 virus challenge in influenza-immune ferrets. Indeed, previous exposure to certain strains could enhance immunogenicity: The strongest HA stem?directed immune response was observed in ferrets previously infected with a divergent 1934 H1N1 virus. These findings suggest that broadly neutralizing antibodies against the conserved stem region of HA can be elicited through vaccination despite previous influenza exposure, which supports the feasibility of developing stem-directed universal influenza vaccines for humans.
Copyright ? 2012, American Association for the Advancement of Science
http://stm.sciencemag.org/content/4/147/147ra114
Vol. 4, Issue 147, p. 147ra114
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3004273
Research Article
Influenza
Elicitation of Broadly Neutralizing Influenza Antibodies in Animals with Previous Influenza Exposure
Chih-Jen Wei1,
Hadi M. Yassine1,
Patrick M. McTamney1,
Jason G. D. Gall2,
James R. R. Whittle1,
Jeffrey C. Boyington1 and
Gary J. Nabel1,*
+ Author Affiliations
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892?3005, USA.
2GenVec Inc., Gaithersburg, MD 20878, USA.
↵*To whom correspondence should be addressed. E-mail: gnabel@nih.gov
Abstract
The immune system responds to influenza infection by producing neutralizing antibodies to the viral surface protein, hemagglutinin (HA), which regularly changes its antigenic structure. Antibodies that target the highly conserved stem region of HA neutralize diverse influenza viruses and can be elicited through vaccination in animals and humans. Efforts to develop universal influenza vaccines have focused on strategies to elicit such antibodies; however, the concern has been raised that previous influenza immunity may abrogate the induction of such broadly protective antibodies. We show here that prime-boost immunization can induce broadly neutralizing antibody responses in influenza-immune mice and ferrets that were previously infected or vaccinated. HA stem?directed antibodies were elicited in mice primed with a DNA vaccine and boosted with inactivated vaccine from H1N1 A/New Caledonia/20/1999 (1999 NC) HA regardless of preexposure. Similarly, gene-based vaccination with replication-defective adenovirus 28 (rAd28) and 5 (rAd5) vectors encoding 1999 NC HA elicited stem-directed neutralizing antibodies and conferred protection against unmatched 1934 and 2007 H1N1 virus challenge in influenza-immune ferrets. Indeed, previous exposure to certain strains could enhance immunogenicity: The strongest HA stem?directed immune response was observed in ferrets previously infected with a divergent 1934 H1N1 virus. These findings suggest that broadly neutralizing antibodies against the conserved stem region of HA can be elicited through vaccination despite previous influenza exposure, which supports the feasibility of developing stem-directed universal influenza vaccines for humans.
Copyright ? 2012, American Association for the Advancement of Science
http://stm.sciencemag.org/content/4/147/147ra114