A Novel R848-Conjugated Inactivated Influenza Virus Vaccine Is Efficacious and Safe in a Neonate Nonhuman Primate Model.
Influenza virus infection of neonates poses a major health concern, often resulting in severe disease and hospitalization. At present, vaccines for this at-risk population are lacking. Thus, development of an effective vaccine is an urgent need. In this study, we have used an innovative nonhuman primate neonate challenge model to test the efficacy of a novel TLR 7/8 agonist R848-conjugated influenza virus vaccine. The use of the intact virus represents a step forward in conjugate vaccine design because it provides multiple antigenic targets allowing for elicitation of a broad immune response. Our results show that this vaccine induces high-level virus-specific Ab- and cell-mediated responses in neonates that result in increased virus clearance and reduced lung pathology postchallenge compared with the nonadjuvanted virus vaccine. Surprisingly, the addition of a second TLR agonist (flagellin) did not enhance vaccine protection, suggesting that combinations of TLR that provide increased efficacy must be determined empirically. These data support further exploration of this new conjugate influenza vaccine approach as a platform for use in the at-risk neonate population.
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101;
Beth C
BC
Holbrook
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101;
Jong R
0000-0003-1519-3274
JR
Kim
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101;
Lance K
LK
Blevins
Department of Pathology, Section of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157;
Matthew J
MJ
Jorgensen
Department of Pathology, Section of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157;
Nancy D
ND
Kock
Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157;
Ralph B
RB
D'Agostino
Animal Resources Program, Wake Forest School of Medicine, Winston-Salem, NC 27157; and.
S Tyler
ST
Aycock
Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109.
Mallinath B
MB
Hadimani
Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109.
S Bruce
0000-0002-8647-8026
SB
King
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101;
Griffith D
GD
Parks
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27101; marthaam@wakehealth.edu.
Martha A
MA
Alexander-Miller
D000818:Animals; D000831:Animals, Newborn; D000914:Antibodies, Viral / Q000032:analysis; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005408:Flagellin / Q000008:administration & dosage; D007093:Imidazoles / Q000008:administration & dosage*; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D009976:Orthomyxoviridae Infections; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000378:metabolism; D015164:Vaccines, Inactivated / Q000276:immunology*
D000914:Antibodies, Viral; D007093:Imidazoles; D007252:Influenza Vaccines; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D015164:Vaccines, Inactivated; D005408:Flagellin; C402365:resiquimod