Stabilization of influenza vaccine enhances protection by microneedle delivery in the mouse skin.
BACKGROUND
Simple and effective vaccine administration is particularly important for annually recommended influenza vaccination. We hypothesized that vaccine delivery to the skin using a patch containing vaccine-coated microneedles could be an attractive approach to improve influenza vaccination compliance and efficacy.


RESULTS
Solid microneedle arrays coated with inactivated influenza vaccine were prepared for simple vaccine delivery to the skin. However, the stability of the influenza vaccine, as measured by hemagglutination activity, was found to be significantly damaged during microneedle coating. The addition of trehalose to the microneedle coating formulation retained hemagglutination activity, indicating stabilization of the coated influenza vaccine. For both intramuscular and microneedle skin immunization, delivery of un-stabilized vaccine yielded weaker protective immune responses including viral neutralizing antibodies, protective efficacies, and recall immune responses to influenza virus. Immunization using un-stabilized vaccine also shifted the pattern of antibody isotypes compared to the stabilized vaccine. Importantly, a single microneedle-based vaccination using stabilized influenza vaccine was found to be superior to intramuscular immunization in controlling virus replication as well as in inducing rapid recall immune responses post challenge.


CONCLUSIONS
The functional integrity of hemagglutinin is associated with inducing improved protective immunity against influenza. Simple microneedle influenza vaccination in the skin produced superior protection compared to conventional intramuscular immunization. This approach is likely to be applicable to other vaccines too.
Department of Microbiology and Immunology, and Yerkes Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Fu-Shi
FS
Quan
Yeu-Chun
YC
Kim
Dae-Goon
DG
Yoo
Richard W
RW
Compans
Mark R
MR
Prausnitz
Sang-Moo
SM
Kang
D000818:Animals; D016503:Drug Delivery Systems; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007271:Injections, Intradermal / Q000009:adverse effects / Q000295:instrumentation*; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D009339:Needles / Q000009:adverse effects; D012867:Skin / Q000378:metabolism*; D014199:Trehalose; D014611:Vaccination / Q000379:methods*
D007074:Immunoglobulin G; D007252:Influenza Vaccines; D014199:Trehalose