tetano
Editor, Senior Moderator
J Virol. 2010 Aug 4. [Epub ahead of print]
Recombinant soluble, multimeric HA and NA exhibit distinctive types of protection against pandemic swine-origin 2009 A(H1N1) influenza virus infection in ferrets.
Bosch BJ, Bodewes R, de Vries RP, Kreijtz JH, Bartelink W, van Amerongen G, Rimmelzwaan GF, de Haan CA, Osterhaus AD, Rottier PJ.
Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht, The Netherlands; Institute of Virology and WHO National Influenza Centre, Erasmus Medical Centre Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Abstract
The emergence and subsequent swift and global spread of the swine-origin influenza virus A(H1N1) in 2009 once again emphasizes the strong need for effective vaccines that can be developed rapidly and applied safely. With this aim we produced soluble, multimeric forms of the 2009 A(H1N1) HA (sHA3) and NA (sNA4) surface glycoproteins using a virus-free mammalian expression system and evaluated their efficacy as vaccines in ferrets. Immunization twice with 3.75-mug doses of these antigens elicited strong antibody responses, which were adjuvant-dependent. Interestingly, co-administration of both antigens strongly enhanced the HA-specific, not the NA-specific responses. Distinct patterns of protection were observed upon challenge inoculation with the homologous H1N1 virus. Whereas vaccination with sHA3 dramatically reduced virus replication - e.g. by lowering pulmonary titers by about 5 log10 units -, immunization with sNA4 markedly decreased the clinical effects of infection such as body weight loss and lung pathology. Clearly, optimal protection was achieved by the combination of the two antigens. Our observations demonstrate the great vaccine potential of multimeric HA and NA ectodomains, as these can be easily, rapidly, flexibly and safely produced in high quantities. In particular our study underscores the underrated importance of NA in influenza vaccination, which we found to profoundly and specifically contribute to protection by HA. Its inclusion in a vaccine is likely to reduce the HA dose required and to broaden the protective immunity.
PMID: 20686020 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20686020
Recombinant soluble, multimeric HA and NA exhibit distinctive types of protection against pandemic swine-origin 2009 A(H1N1) influenza virus infection in ferrets.
Bosch BJ, Bodewes R, de Vries RP, Kreijtz JH, Bartelink W, van Amerongen G, Rimmelzwaan GF, de Haan CA, Osterhaus AD, Rottier PJ.
Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht, The Netherlands; Institute of Virology and WHO National Influenza Centre, Erasmus Medical Centre Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Abstract
The emergence and subsequent swift and global spread of the swine-origin influenza virus A(H1N1) in 2009 once again emphasizes the strong need for effective vaccines that can be developed rapidly and applied safely. With this aim we produced soluble, multimeric forms of the 2009 A(H1N1) HA (sHA3) and NA (sNA4) surface glycoproteins using a virus-free mammalian expression system and evaluated their efficacy as vaccines in ferrets. Immunization twice with 3.75-mug doses of these antigens elicited strong antibody responses, which were adjuvant-dependent. Interestingly, co-administration of both antigens strongly enhanced the HA-specific, not the NA-specific responses. Distinct patterns of protection were observed upon challenge inoculation with the homologous H1N1 virus. Whereas vaccination with sHA3 dramatically reduced virus replication - e.g. by lowering pulmonary titers by about 5 log10 units -, immunization with sNA4 markedly decreased the clinical effects of infection such as body weight loss and lung pathology. Clearly, optimal protection was achieved by the combination of the two antigens. Our observations demonstrate the great vaccine potential of multimeric HA and NA ectodomains, as these can be easily, rapidly, flexibly and safely produced in high quantities. In particular our study underscores the underrated importance of NA in influenza vaccination, which we found to profoundly and specifically contribute to protection by HA. Its inclusion in a vaccine is likely to reduce the HA dose required and to broaden the protective immunity.
PMID: 20686020 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20686020