TY - JOUR
T1 - Cooperativity Between CD8+ T Cells, Non-Neutralizing Antibodies, and Alveolar Macrophages Is Important for Heterosubtypic Influenza Virus Immunity
AU - Laidlaw, Brian J.
AU - Decman, Vilma
AU - Ali, Mohammed Alkhatim A.
AU - Abt, Michael C.
AU - Wolf, Amaya I.
AU - Monticelli, Laurel A.
AU - Mozdzanowska, Krystyna
AU - Angelosanto, Jill M.
AU - Artis, David
AU - Erikson, Jan
AU - Wherry, E. John
PY - 2013
Y1 - 2013
N2 - Seasonal epidemics of influenza virus result in ~36,000 deaths annually in the United States. Current vaccines against influenza virus elicit an antibody response specific for the envelope glycoproteins. However, high mutation rates result in the emergence of new viral serotypes, which elude neutralization by preexisting antibodies. T lymphocytes have been reported to be capable of mediating heterosubtypic protection through recognition of internal, more conserved, influenza virus proteins. Here, we demonstrate using a recombinant influenza virus expressing the LCMV GP33-41 epitope that influenza virus-specific CD8+ T cells and virus-specific non-neutralizing antibodies each are relatively ineffective at conferring heterosubtypic protective immunity alone. However, when combined virus-specific CD8 T cells and non-neutralizing antibodies cooperatively elicit robust protective immunity. This synergistic improvement in protective immunity is dependent, at least in part, on alveolar macrophages and/or other lung phagocytes. Overall, our studies suggest that an influenza vaccine capable of eliciting both CD8+ T cells and antibodies specific for highly conserved influenza proteins may be able to provide heterosubtypic protection in humans, and act as the basis for a potential "universal" vaccine.
AB - Seasonal epidemics of influenza virus result in ~36,000 deaths annually in the United States. Current vaccines against influenza virus elicit an antibody response specific for the envelope glycoproteins. However, high mutation rates result in the emergence of new viral serotypes, which elude neutralization by preexisting antibodies. T lymphocytes have been reported to be capable of mediating heterosubtypic protection through recognition of internal, more conserved, influenza virus proteins. Here, we demonstrate using a recombinant influenza virus expressing the LCMV GP33-41 epitope that influenza virus-specific CD8+ T cells and virus-specific non-neutralizing antibodies each are relatively ineffective at conferring heterosubtypic protective immunity alone. However, when combined virus-specific CD8 T cells and non-neutralizing antibodies cooperatively elicit robust protective immunity. This synergistic improvement in protective immunity is dependent, at least in part, on alveolar macrophages and/or other lung phagocytes. Overall, our studies suggest that an influenza vaccine capable of eliciting both CD8+ T cells and antibodies specific for highly conserved influenza proteins may be able to provide heterosubtypic protection in humans, and act as the basis for a potential "universal" vaccine.
UR - http://www.scopus.com/inward/record.url?scp=84875992924&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1003207
DO - 10.1371/journal.ppat.1003207
M3 - Article
C2 - 23516357
AN - SCOPUS:84875992924
SN - 1553-7366
VL - 9
JO - PLoS pathogens
JF - PLoS pathogens
IS - 3
M1 - e1003207
ER -