Antibody contributes to heterosubtypic protection against influenza A-induced tachypnea in cotton rats.
BACKGROUND
Influenza virus infection or vaccination evokes an antibody response to viral hemagglutinin (HA) and neuraminidase (NA) surface glycoproteins, which results in immunity against influenza A viruses of the same HA and NA subtype. A heterosubtypic immune response that offers some protection against different influenza A subtypes has been suggested from epidemiologic studies in human influenza outbreaks, and has been induced in experimental animal models. Original studies of such cross-protection showed that cytotoxic T lymphocytes (CTL) protect H3N2-immune mice from a lethal H1N1 infection. More recent studies in mice demonstrate that antibodies also contribute to heterosubtypic immunity (HSI). We previously demonstrated that HSI in cotton rats (Sigmodon hispidus) is characterized by protection of H3N2-immune animals from influenza H1N1-induced increase in respiratory rate (tachypnea). Alternatively, H1N1-immune animals are protected from H3N2-induced tachypnea. The experiments described in this report were designed to elucidate the immune mechanism that prevents this very early sign of disease.


RESULTS
Our results show that cotton rats provided with H1N1-immune serum prior to challenge with an H3N2 virus were protected from influenza-associated tachypnea, with the degree of protection correlating with the antibody titer transferred. Immunization with an inactivated preparation of virus delivered intramuscularly also provided some protection suggesting that CTL and/or mucosal antibody responses are not required for protection. Antibodies specific for conserved epitopes present on the virus exterior are likely to facilitate this protection since prophylactic treatment of cotton rats with anti-M2e (the extracellular domain of M2) but not anti-nucleoprotein (NP) reduced virus-induced tachypnea.


CONCLUSIONS
In the cotton rat model of heterosubtypic immunity, humoral immunity plays a role in protecting animals from influenza-induced tachypea. Partial protection against respiratory disease caused by different influenza A subtypes can be attained with either live virus administered intranasally or inactivated virus delivered intramuscularly suggesting that either vaccine regimen may provide some protection against potential pandemic outbreaks in humans.
Straight
Timothy M
TM
Department of Clinical Investigation, Brooke Army Medical Center, Fort Sam Houston, TX, USA. Timothy.Straight@amedd.army.mil
Ottolini
Martin G
MG
Prince
Gregory A
GA
Eichelberger
Maryna C
MC
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D003429:Cross Reactions; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D008297:Male; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000503:physiopathology* / Q000517:prevention & control / Q000821:virology; D012120:Respiration Disorders / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control* / Q000821:virology; D016205:Sigmodontinae
D000914:Antibodies, Viral; D007106:Immune Sera; D007252:Influenza Vaccines