Fc receptor is not required for inducing antibodies but plays a critical role in conferring protection after influenza M2 vaccination.
The ectodomain of matrix protein 2 (M2e) of influenza virus is considered a rational target for a universal influenza A vaccine. To better understand M2e immune-mediated protection, Fc receptor common γ chain deficient (FcRγ(-/-) ) and wild-type mice were immunized with a tandem repeat of M2e presented on virus-like particles (M2e5x VLP). Levels of M2e-specific antibodies that were induced in FcRγ(-/-) mice after immunization with M2e5x VLP were similar to those in wild-type mice. In addition, M2e antibodies induced in FcRγ(-/-) mice were found to be equally protective as those induced in wild-type mice. However, M2e5x VLP-immunized FcRγ(-/-) mice were not well protected, as shown by severe weight loss, higher lung viral titres and interleukin-6 inflammatory cytokine production upon influenza virus challenge compared with M2e5x VLP-immunized wild-type mice. Importantly, FcRγ(-/-) mice that were immunized with inactivated influenza virus induced haemagglutination inhibition activity and were well protected without a significant weight loss. Interestingly, interferon-γ-producing CD4 T and CD8 T cells were found to be prevalent in lungs from M2e5x VLP-immunized FcRγ(-/-) mice, which appeared to be correlated with a faster recovery after infection. These results indicate that Fc receptors play a primary role in conferring M2e-specific antibody-mediated protection whereas T cells may contribute to the recovery at later stages of infection.
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
Yu-Na
YN
Lee
Young-Tae
YT
Lee
Min-Chul
MC
Kim
Hye Suk
HS
Hwang
Jong Seok
JS
Lee
Ki-Hye
KH
Kim
Sang-Moo
SM
Kang
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006384:Hemagglutination; D018836:Inflammation Mediators / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012074:Remission Induction; D013997:Time Factors; D014611:Vaccination; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000008:administration & dosage / Q000276:immunology*; D015431:Weight Loss; D000086082:Viroporin Proteins
D000914:Antibodies, Viral; D018836:Inflammation Mediators; D007252:Influenza Vaccines; D007371:Interferon-gamma; D015850:Interleukin-6; D017452:Receptors, IgG; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C577686:interleukin-6, mouse
Fc receptor; T cells; influenza virus; matrix protein 2 ectodomain antibodies; matrix protein 2 ectodomain virus-like particles