Microneedle delivery of H5N1 influenza virus-like particles to the skin induces long-lasting B- and T-cell responses in mice.
A simple method suitable for self-administration of vaccine would improve mass immunization, particularly during a pandemic outbreak. Influenza virus-like particles (VLPs) have been suggested as promising vaccine candidates against potentially pandemic influenza viruses, as they confer long-lasting immunity but are not infectious. We investigated the immunogenicity and protective efficacy of influenza H5 VLPs containing the hemagglutinin (HA) of A/Vietnam/1203/04 (H5N1) virus delivered into the skin of mice using metal microneedle patches and also studied the response of Langerhans cells in a human skin model. Prime-boost microneedle vaccinations with H5 VLPs elicited higher levels of virus-specific IgG1 and IgG2a antibodies, virus-specific antibody-secreting cells, and cytokine-producing cells up to 8 months after vaccination compared to the same antigen delivered intramuscularly. Both prime-boost microneedle and intramuscular vaccinations with H5 VLPs induced similar hemagglutination inhibition titers and conferred 100% protection against lethal challenge with the wild-type A/Vietnam/1203/04 virus 16 weeks after vaccination. Microneedle delivery of influenza VLPs to viable human skin using microneedles induced the movement of CD207(+) Langerhans cells toward the basement membrane. Microneedle vaccination in the skin with H5 VLPs represents a promising approach for a self-administered vaccine against viruses with pandemic potential.
Song
Jae-Min
JM
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
Kim
Yeu-Chun
YC
Lipatov
Aleksandr S
AS
Pearton
Marc
M
Davis
C Todd
CT
Yoo
Dae-Goon
DG
Park
Kyoung-Mi
KM
Chen
Li-Mei
LM
Quan
Fu-Shi
FS
Birchall
James C
JC
Donis
Ruben O
RO
Prausnitz
Mark R
MR
Compans
Richard W
RW
Kang
Sang-Moo
SM
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006389:Hemagglutinins, Viral / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D066298:In Vitro Techniques; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D007801:Langerhans Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009339:Needles; D012867:Skin / Q000276:immunology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination / Q000379:methods; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000276:immunology
D000914:Antibodies, Viral; D016207:Cytokines; D006389:Hemagglutinins, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D022721:Vaccines, Virosome; C458881:hemagglutinin fusogenic peptide, influenza virus