tetano
Editor, Senior Moderator
J Virol. 2011 Mar 2. [Epub ahead of print]
Regulation of anti-nucleoprotein IgG by systemic vaccination and its effect on influenza virus clearance.
Lamere MW, Moquin A, Lee FE, Misra RS, Blair PJ, Haynes L, Randall TD, Lund FE, Kaminski DA.
Department of Medicine, Division of Clinical Immunology and Rheumatology; University of Rochester Medical Center, Rochester, NY 14642; Trudeau Institute, Saranac Lake, NY 12983; Respiratory Diseases Research Department, Naval Health Research Center, San Diego, CA 92106.
Abstract
Seasonal influenza epidemics recur due to antigenic drift of envelope glycoprotein antigens and immune evasion of circulating viruses. Additionally, antigenic shift can lead to influenza pandemics. Thus, a universal vaccine that protects against multiple influenza strains could alleviate the continuing impact of this virus on human health. In mice, accelerated clearance of a new viral strain (cross-protection) can be elicited by prior infection (heterosubtypic immunity) or by immunization with the highly conserved internal nucleoprotein (NP). Both heterosubtypic immunity and NP-immune protection require antibody production. Here, we show that systemic immunization with NP readily accelerated clearance of a 2009 pandemic H1N1 influenza isolate in an antibody-dependent manner. However, human immunization with trivalent-inactivated influenza vaccine (TIV) only rarely and modestly boosted existing levels of anti-NP IgG. Similar results were observed in mice, although the reaction could be enhanced with adjuvants, by adjusting the stoichiometry among NP and other vaccine components, and by increasing the interval between TIV prime and boost. Importantly, mouse heterosubtypic immunity that had waned over several months could be enhanced by injecting purified anti-NP IgG or by boosting with NP protein, correlating with a long-lived increase in anti-NP antibody titers. Thus, current immunization strategies poorly induce NP-immune antibody that is nonetheless capable of contributing to long-lived cross-protection. The high conservation of NP antigen and the known longevity of antibody responses suggest that the antiviral activity of anti-NP IgG may provide a critically needed component of a universal influenza vaccine.
PMID: 21367900 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21367900
Regulation of anti-nucleoprotein IgG by systemic vaccination and its effect on influenza virus clearance.
Lamere MW, Moquin A, Lee FE, Misra RS, Blair PJ, Haynes L, Randall TD, Lund FE, Kaminski DA.
Department of Medicine, Division of Clinical Immunology and Rheumatology; University of Rochester Medical Center, Rochester, NY 14642; Trudeau Institute, Saranac Lake, NY 12983; Respiratory Diseases Research Department, Naval Health Research Center, San Diego, CA 92106.
Abstract
Seasonal influenza epidemics recur due to antigenic drift of envelope glycoprotein antigens and immune evasion of circulating viruses. Additionally, antigenic shift can lead to influenza pandemics. Thus, a universal vaccine that protects against multiple influenza strains could alleviate the continuing impact of this virus on human health. In mice, accelerated clearance of a new viral strain (cross-protection) can be elicited by prior infection (heterosubtypic immunity) or by immunization with the highly conserved internal nucleoprotein (NP). Both heterosubtypic immunity and NP-immune protection require antibody production. Here, we show that systemic immunization with NP readily accelerated clearance of a 2009 pandemic H1N1 influenza isolate in an antibody-dependent manner. However, human immunization with trivalent-inactivated influenza vaccine (TIV) only rarely and modestly boosted existing levels of anti-NP IgG. Similar results were observed in mice, although the reaction could be enhanced with adjuvants, by adjusting the stoichiometry among NP and other vaccine components, and by increasing the interval between TIV prime and boost. Importantly, mouse heterosubtypic immunity that had waned over several months could be enhanced by injecting purified anti-NP IgG or by boosting with NP protein, correlating with a long-lived increase in anti-NP antibody titers. Thus, current immunization strategies poorly induce NP-immune antibody that is nonetheless capable of contributing to long-lived cross-protection. The high conservation of NP antigen and the known longevity of antibody responses suggest that the antiviral activity of anti-NP IgG may provide a critically needed component of a universal influenza vaccine.
PMID: 21367900 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21367900