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Transdermal influenza immunization with vaccine-coated microneedle arrays.

Koutsonanos DG, del Pilar Martin M, Zarnitsyn VG, Sullivan SP, Compans RW, Prausnitz MR, Skountzou I - PLoS ONE (2009)

Bottom Line: Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose.Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells.In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a novel and highly effective immunization method.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology & Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.

ABSTRACT

Background: Influenza is a contagious disease caused by a pathogenic virus, with outbreaks all over the world and thousands of hospitalizations and deaths every year. Due to virus antigenic drift and short-lived immune responses, annual vaccination is required. However, vaccine coverage is incomplete, and improvement in immunization is needed. The objective of this study is to investigate a novel method for transdermal delivery using metal microneedle arrays (MN) coated with inactivated influenza virus to determine whether this route is a simpler and safer approach than the conventional immunization, capable to induce robust immune responses and confer protection against lethal virus challenge.

Methodology/principal findings: Inactivated A/Aichi/2/68 (H3N2) influenza virus was coated on metal microneedle arrays and applied to mice as a vaccine in the caudal dorsal skin area. Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose. Challenge studies in mice with 5 x LD(50) of mouse adapted Aichi virus demonstrated complete protection. Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells. In addition, the use of MN showed a dose-sparing effect and a strong Th2 bias when compared to an intramuscular (IM) reference immunization.

Conclusions/significance: The present results show that delivery of inactivated influenza virus through the skin using metal microneedle arrays induced strong humoral and cellular immune responses capable of conferring protection against virus challenge as efficiently as intramuscular immunization, which is the standard vaccination route. In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a novel and highly effective immunization method.

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Related in: MedlinePlus

Total anti-influenza serum IgG and isotype profiles after intramuscular (IM) and microneedle (MN) immunization with 3 µg or 10 µg of inactivated influenza virus compared to naïve control group (N).(A) Total serum IgG titers determined on days 14 and 28 after immunization. (B) Serum IgG2a and IgG1 isotypes on day 14 and (C) Serum IgG2a and IgG1 isotypes on day 28. (D) Ratio of IgG1/IgG2a on day 14 (E) Ratio of IgG1/IgG2a on day 28. All IgG measurements were made by quantitative ELISA (average±s.e) ap<0.05 when IM 10 µg compared to the IM 3 µg group.
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pone-0004773-g003: Total anti-influenza serum IgG and isotype profiles after intramuscular (IM) and microneedle (MN) immunization with 3 µg or 10 µg of inactivated influenza virus compared to naïve control group (N).(A) Total serum IgG titers determined on days 14 and 28 after immunization. (B) Serum IgG2a and IgG1 isotypes on day 14 and (C) Serum IgG2a and IgG1 isotypes on day 28. (D) Ratio of IgG1/IgG2a on day 14 (E) Ratio of IgG1/IgG2a on day 28. All IgG measurements were made by quantitative ELISA (average±s.e) ap<0.05 when IM 10 µg compared to the IM 3 µg group.

Mentions: We also measured the circulating levels of influenza-specific IgG in sera by ELISA (Fig. 3). We observed a substantial increase in influenza virus-specific IgG levels 14 days after immunization in the sera of immunized mice as compared to the naïve group (p<0.001) (Figure 3A). By day 28, the anti-Aichi antibody titers further increased twofold in the immunized mice with the exception of the 3 µg IM immunized group. We only observed a dose-dependent increase in response for the IM group. The high IgG titers obtained by MN delivery at both doses suggest that it performs better than IM injection at low doses.


Transdermal influenza immunization with vaccine-coated microneedle arrays.

Koutsonanos DG, del Pilar Martin M, Zarnitsyn VG, Sullivan SP, Compans RW, Prausnitz MR, Skountzou I - PLoS ONE (2009)

Total anti-influenza serum IgG and isotype profiles after intramuscular (IM) and microneedle (MN) immunization with 3 µg or 10 µg of inactivated influenza virus compared to naïve control group (N).(A) Total serum IgG titers determined on days 14 and 28 after immunization. (B) Serum IgG2a and IgG1 isotypes on day 14 and (C) Serum IgG2a and IgG1 isotypes on day 28. (D) Ratio of IgG1/IgG2a on day 14 (E) Ratio of IgG1/IgG2a on day 28. All IgG measurements were made by quantitative ELISA (average±s.e) ap<0.05 when IM 10 µg compared to the IM 3 µg group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2651574&req=5

pone-0004773-g003: Total anti-influenza serum IgG and isotype profiles after intramuscular (IM) and microneedle (MN) immunization with 3 µg or 10 µg of inactivated influenza virus compared to naïve control group (N).(A) Total serum IgG titers determined on days 14 and 28 after immunization. (B) Serum IgG2a and IgG1 isotypes on day 14 and (C) Serum IgG2a and IgG1 isotypes on day 28. (D) Ratio of IgG1/IgG2a on day 14 (E) Ratio of IgG1/IgG2a on day 28. All IgG measurements were made by quantitative ELISA (average±s.e) ap<0.05 when IM 10 µg compared to the IM 3 µg group.
Mentions: We also measured the circulating levels of influenza-specific IgG in sera by ELISA (Fig. 3). We observed a substantial increase in influenza virus-specific IgG levels 14 days after immunization in the sera of immunized mice as compared to the naïve group (p<0.001) (Figure 3A). By day 28, the anti-Aichi antibody titers further increased twofold in the immunized mice with the exception of the 3 µg IM immunized group. We only observed a dose-dependent increase in response for the IM group. The high IgG titers obtained by MN delivery at both doses suggest that it performs better than IM injection at low doses.

Bottom Line: Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose.Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells.In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a novel and highly effective immunization method.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology & Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.

ABSTRACT

Background: Influenza is a contagious disease caused by a pathogenic virus, with outbreaks all over the world and thousands of hospitalizations and deaths every year. Due to virus antigenic drift and short-lived immune responses, annual vaccination is required. However, vaccine coverage is incomplete, and improvement in immunization is needed. The objective of this study is to investigate a novel method for transdermal delivery using metal microneedle arrays (MN) coated with inactivated influenza virus to determine whether this route is a simpler and safer approach than the conventional immunization, capable to induce robust immune responses and confer protection against lethal virus challenge.

Methodology/principal findings: Inactivated A/Aichi/2/68 (H3N2) influenza virus was coated on metal microneedle arrays and applied to mice as a vaccine in the caudal dorsal skin area. Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose. Challenge studies in mice with 5 x LD(50) of mouse adapted Aichi virus demonstrated complete protection. Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells. In addition, the use of MN showed a dose-sparing effect and a strong Th2 bias when compared to an intramuscular (IM) reference immunization.

Conclusions/significance: The present results show that delivery of inactivated influenza virus through the skin using metal microneedle arrays induced strong humoral and cellular immune responses capable of conferring protection against virus challenge as efficiently as intramuscular immunization, which is the standard vaccination route. In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a novel and highly effective immunization method.

Show MeSH
Related in: MedlinePlus