Serological memory and long-term protection to novel H1N1 influenza virus after skin vaccination

Department of Microbiology & Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
The Journal of Infectious Diseases (Impact Factor: 5.78). 06/2011; 204(4):582-91. DOI: 10.1093/infdis/jir094
Source: PubMed

ABSTRACT A major goal in influenza vaccine development is induction of serological memory and cellular responses to confer long-term protection and limit virus spread after infection. Here, we investigate induction of long-lived immunity against the 2009 H1N1 virus after skin vaccination.
BALB/c mice received a single dose of 5 μg inactivated A/California/04/09 virus via coated metal microneedles (MN) applied to skin or via subcutaneous injection.
MN or subcutaneous vaccination elicited similar serum IgG and hemagglutination inhibition titers and 100% protection against lethal viral challenge 6 weeks after vaccination. Six months after vaccination, the subcutaneous group exhibited a 60% decrease in functional antibody titers and extensive lung inflammation after challenge with 10 × LD(50) of homologous virus. In contrast, the MN group maintained high functional antibody titers and IFN-γ levels, inhibition of viral replication, and no signs of lung inflammation after challenge. MN vaccination conferred complete protection against lethal challenge, whereas subcutaneous vaccination induced only partial protection. These findings were further supported by high numbers of bone marrow plasma cells and spleen antibody-secreting cells detected in the MN group.
A single skin vaccination with MN induced potent long-lived immunity and improved protection against the 2009 H1N1 influenza virus, compared with subcutaneous injection.

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    • "vaccines or drugs into the epidermis and dermis of the skin (Fig. 1), rather than intramuscularly, the typical route. Intradermal delivery of influenza vaccine by microneedles can lead to longer-lasting and more-robust antibody responses than intramuscular vaccination in mice, suggesting the possibility of improved efficacy [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]. Clinical studies comparing intramuscular delivery of influenza vaccine to intradermal delivery in liquid form through hollow minineedles and microneedles have shown a superior immune response in the elderly when an equal dose is administered intradermally, and equivalent immune responses in younger adults with administration of a reduced dose [18] [19] [20] [21] [22] [23] [24]. "
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