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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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Antibody secreting cells (ASC) in spleens and lungs of immunized mice.(A) Splenocytes and (B) single cell suspensions from lungs of immunized mice were assessed by ELISPOT assay for anti-influenza IgG ASC and compared with (N) naïve control, and (Inf.) unimmunized infected groups 4 days post–challenge (average±s.e). ap<0.05 when MN 3 µg compared to the IM 3 µg group. bp<0.05 when MN 10 µg compared to the IM 3 µg group.
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pone-0004773-g007: Antibody secreting cells (ASC) in spleens and lungs of immunized mice.(A) Splenocytes and (B) single cell suspensions from lungs of immunized mice were assessed by ELISPOT assay for anti-influenza IgG ASC and compared with (N) naïve control, and (Inf.) unimmunized infected groups 4 days post–challenge (average±s.e). ap<0.05 when MN 3 µg compared to the IM 3 µg group. bp<0.05 when MN 10 µg compared to the IM 3 µg group.

Mentions: The sustained humoral immune responses that confer protection against influenza infection are attributed in part to long-lived antibody-secreting cells (ASC). Eight weeks after the immunization and shortly after challenge, the mice were examined for ASC in spleen and lungs. In spleen, anti-Aichi IgG ASC were only elevated in MN and IM groups which received the 10 µg dose, with no significant differences among these groups. Antigen-secreting cell numbers were very low in all other groups including immunized, naïve or infected mice (Figure 7A).


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)

Antibody secreting cells (ASC) in spleens and lungs of immunized mice.(A) Splenocytes and (B) single cell suspensions from lungs of immunized mice were assessed by ELISPOT assay for anti-influenza IgG ASC and compared with (N) naïve control, and (Inf.) unimmunized infected groups 4 days post–challenge (average±s.e). ap<0.05 when MN 3 µg compared to the IM 3 µg group. bp<0.05 when MN 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-g007: Antibody secreting cells (ASC) in spleens and lungs of immunized mice.(A) Splenocytes and (B) single cell suspensions from lungs of immunized mice were assessed by ELISPOT assay for anti-influenza IgG ASC and compared with (N) naïve control, and (Inf.) unimmunized infected groups 4 days post–challenge (average±s.e). ap<0.05 when MN 3 µg compared to the IM 3 µg group. bp<0.05 when MN 10 µg compared to the IM 3 µg group.
Mentions: The sustained humoral immune responses that confer protection against influenza infection are attributed in part to long-lived antibody-secreting cells (ASC). Eight weeks after the immunization and shortly after challenge, the mice were examined for ASC in spleen and lungs. In spleen, anti-Aichi IgG ASC were only elevated in MN and IM groups which received the 10 µg dose, with no significant differences among these groups. Antigen-secreting cell numbers were very low in all other groups including immunized, naïve or infected mice (Figure 7A).

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