TY - JOUR
T1 - Heterologous viral protein interactions within licensed seasonal influenza virus vaccines
AU - Koroleva, Marina
AU - Batarse, Frances
AU - Moritzky, Savannah
AU - Henry, Carole
AU - Chaves, Francisco
AU - Wilson, Patrick
AU - Krammer, Florian
AU - Richards, Katherine
AU - Sant, Andrea J.
N1 - Funding Information:
The Icahn School of Medicine at Mount Sinai has filed patent applications on influenza virus vaccines that name F.K. as inventor. The Krammer laboratory has received funding from GlaxoSmithKline for an unrelated influenza virus vaccine project.
Funding Information:
This project has been funded with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under CEIRS Contract No. HHSN272201400005C awarded to A.J.S., P.W., and C.H. and CEIRS Contract No, HHSN272201400008C awarded to F.K. This work has been supported in part by an Institutional Program Unifying Population and Laboratory Based Sciences Award from the Burroughs Wellcome Fund to SM.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Currently, licensed influenza virus vaccines are designed and tested only for their ability to elicit hemagglutinin (HA)-reactive, neutralizing antibodies. Despite this, the purification process in vaccine manufacturing often does not completely remove other virion components. In the studies reported here, we have examined the viral protein composition of a panel of licensed vaccines from different manufacturers and licensed in different years. Using western blotting, we found that, beyond HA proteins, there are detectable quantities of neuraminidase (NA), nucleoprotein (NP), and matrix proteins (M1) from both influenza A and influenza B viruses in the vaccines but that the composition differed by source and method of vaccine preparation. We also found that disparities in viral protein composition were associated with distinct patterns of elicited antibody specificities. Strikingly, our studies also revealed that many viral proteins contained in the vaccine form heterologous complexes. When H1 proteins were isolated by immunoprecipitation, NA (N1), M1 (M1-A), H3, and HA-B proteins were co-isolated with the H1. Further biochemical studies suggest that these interactions persist for at least 4 h at 37 °C and that the membrane/intracytoplasmic domains in the intact HA proteins are important for the intermolecular interactions detected. These studies indicate that, if such interactions persist after vaccines reach the draining lymph node, both dendritic cells and HA-specific B cells may take up multiple viral proteins simultaneously. Whether these interactions are beneficial or harmful to the developing immune response will depend on the functional potential of the elicited virus-specific CD4 T cells.
AB - Currently, licensed influenza virus vaccines are designed and tested only for their ability to elicit hemagglutinin (HA)-reactive, neutralizing antibodies. Despite this, the purification process in vaccine manufacturing often does not completely remove other virion components. In the studies reported here, we have examined the viral protein composition of a panel of licensed vaccines from different manufacturers and licensed in different years. Using western blotting, we found that, beyond HA proteins, there are detectable quantities of neuraminidase (NA), nucleoprotein (NP), and matrix proteins (M1) from both influenza A and influenza B viruses in the vaccines but that the composition differed by source and method of vaccine preparation. We also found that disparities in viral protein composition were associated with distinct patterns of elicited antibody specificities. Strikingly, our studies also revealed that many viral proteins contained in the vaccine form heterologous complexes. When H1 proteins were isolated by immunoprecipitation, NA (N1), M1 (M1-A), H3, and HA-B proteins were co-isolated with the H1. Further biochemical studies suggest that these interactions persist for at least 4 h at 37 °C and that the membrane/intracytoplasmic domains in the intact HA proteins are important for the intermolecular interactions detected. These studies indicate that, if such interactions persist after vaccines reach the draining lymph node, both dendritic cells and HA-specific B cells may take up multiple viral proteins simultaneously. Whether these interactions are beneficial or harmful to the developing immune response will depend on the functional potential of the elicited virus-specific CD4 T cells.
UR - http://www.scopus.com/inward/record.url?scp=85077676987&partnerID=8YFLogxK
U2 - 10.1038/s41541-019-0153-1
DO - 10.1038/s41541-019-0153-1
M3 - Article
AN - SCOPUS:85077676987
SN - 2059-0105
VL - 5
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 3
ER -