Stability kinetics of influenza vaccine coated onto microneedles during drying and storage

Yeu Chun Kim; Fu Shi Quan; Richard W. Compans; Sang Moo Kang; Mark R. Prausnitz

doi:10.1007/s11095-010-0134-6

Stability kinetics of influenza vaccine coated onto microneedles during drying and storage

Yeu Chun Kim
, Fu Shi Quan
, Richard W. Compans
, Sang Moo Kang
, Mark R. Prausnitz

Research output: Contribution to journal › Article › peer-review

95 Citations (Scopus)

Abstract

Purpose: This study sought to determine the effects of microneedle coating formulation, drying time and storage time on antigen stability and in vivo immunogenicity of influenza microneedle vaccines. Methods: The stability of inactivated influenza virus vaccine was monitored by hemagglutination (HA) activity and virus particle aggregation as a function of storage time and temperature with or without trehalose. In vivo immunogenicity of inactivated influenza vaccines coated onto microneedles was determined in mice by virus-specific antibody titers and survival rates. Results: In the absence of trehalose, HA activity decreased below 10% and to almost zero after 1 h and 1 month of drying, respectively. Addition of trehalose maintained HA activity above 60% after drying and above 20% after 1 month storage at 25°C. Loss of HA activity generally correlated with increased virus particle aggregation. Administration of microneedles coated with trehalose-stabilized influenza vaccine yielded high serum IgG antibody titers even after 1 month storage, and all animals survived with minimal weight loss after lethal challenge infection. Conclusions: Inactivated influenza virus vaccine coated on microneedles with trehalose significantly improved the HA activity as well as in vivo immunogenicity of the vaccine after an extended time of storage.

Original language	English
Pages (from-to)	135-144
Number of pages	10
Journal	Pharmaceutical Research
Volume	28
Issue number	1
DOIs	https://doi.org/10.1007/s11095-010-0134-6
Publication status	Published - Jan 2011

Bibliographical note

Funding Information:
This work was carried out at the Emory University School of Medicine and the Georgia Tech Center for Drug Design, Development and Delivery and Institute for Bioengineering and Biosciences. It was supported in part by NIH grants R01-EB006369 (M.R.P.), U01-AI0680003 (R.W.C.), SERCEB (R.W.C) and the Georgia Research Alliance Program grant (S.M.K). We thank Dr. Vladimir Zarnitsyn for microneedle fabrication, Dr. Andrew Lyon for dynamic light scattering assay, and Dr. Mark Allen for laser microfabrication facilities. M.R.P. serves as a consultant and is an inventor on patents licensed to companies developing microneedle-based products. This possible conflict of interest has been disclosed and is being managed by Georgia Tech and Emory University.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

inactivated virus vaccine
influenza virus
long-term stability
microneedle
trehalose

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10.1007/s11095-010-0134-6

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title = "Stability kinetics of influenza vaccine coated onto microneedles during drying and storage",

abstract = "Purpose: This study sought to determine the effects of microneedle coating formulation, drying time and storage time on antigen stability and in vivo immunogenicity of influenza microneedle vaccines. Methods: The stability of inactivated influenza virus vaccine was monitored by hemagglutination (HA) activity and virus particle aggregation as a function of storage time and temperature with or without trehalose. In vivo immunogenicity of inactivated influenza vaccines coated onto microneedles was determined in mice by virus-specific antibody titers and survival rates. Results: In the absence of trehalose, HA activity decreased below 10\% and to almost zero after 1 h and 1 month of drying, respectively. Addition of trehalose maintained HA activity above 60\% after drying and above 20\% after 1 month storage at 25°C. Loss of HA activity generally correlated with increased virus particle aggregation. Administration of microneedles coated with trehalose-stabilized influenza vaccine yielded high serum IgG antibody titers even after 1 month storage, and all animals survived with minimal weight loss after lethal challenge infection. Conclusions: Inactivated influenza virus vaccine coated on microneedles with trehalose significantly improved the HA activity as well as in vivo immunogenicity of the vaccine after an extended time of storage.",

keywords = "inactivated virus vaccine, influenza virus, long-term stability, microneedle, trehalose",

author = "Kim, \{Yeu Chun\} and Quan, \{Fu Shi\} and Compans, \{Richard W.\} and Kang, \{Sang Moo\} and Prausnitz, \{Mark R.\}",

note = "Funding Information: This work was carried out at the Emory University School of Medicine and the Georgia Tech Center for Drug Design, Development and Delivery and Institute for Bioengineering and Biosciences. It was supported in part by NIH grants R01-EB006369 (M.R.P.), U01-AI0680003 (R.W.C.), SERCEB (R.W.C) and the Georgia Research Alliance Program grant (S.M.K). We thank Dr. Vladimir Zarnitsyn for microneedle fabrication, Dr. Andrew Lyon for dynamic light scattering assay, and Dr. Mark Allen for laser microfabrication facilities. M.R.P. serves as a consultant and is an inventor on patents licensed to companies developing microneedle-based products. This possible conflict of interest has been disclosed and is being managed by Georgia Tech and Emory University.",

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doi = "10.1007/s11095-010-0134-6",

language = "English",

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T1 - Stability kinetics of influenza vaccine coated onto microneedles during drying and storage

AU - Kim, Yeu Chun

AU - Quan, Fu Shi

AU - Compans, Richard W.

AU - Kang, Sang Moo

AU - Prausnitz, Mark R.

N1 - Funding Information: This work was carried out at the Emory University School of Medicine and the Georgia Tech Center for Drug Design, Development and Delivery and Institute for Bioengineering and Biosciences. It was supported in part by NIH grants R01-EB006369 (M.R.P.), U01-AI0680003 (R.W.C.), SERCEB (R.W.C) and the Georgia Research Alliance Program grant (S.M.K). We thank Dr. Vladimir Zarnitsyn for microneedle fabrication, Dr. Andrew Lyon for dynamic light scattering assay, and Dr. Mark Allen for laser microfabrication facilities. M.R.P. serves as a consultant and is an inventor on patents licensed to companies developing microneedle-based products. This possible conflict of interest has been disclosed and is being managed by Georgia Tech and Emory University.

PY - 2011/1

Y1 - 2011/1

N2 - Purpose: This study sought to determine the effects of microneedle coating formulation, drying time and storage time on antigen stability and in vivo immunogenicity of influenza microneedle vaccines. Methods: The stability of inactivated influenza virus vaccine was monitored by hemagglutination (HA) activity and virus particle aggregation as a function of storage time and temperature with or without trehalose. In vivo immunogenicity of inactivated influenza vaccines coated onto microneedles was determined in mice by virus-specific antibody titers and survival rates. Results: In the absence of trehalose, HA activity decreased below 10% and to almost zero after 1 h and 1 month of drying, respectively. Addition of trehalose maintained HA activity above 60% after drying and above 20% after 1 month storage at 25°C. Loss of HA activity generally correlated with increased virus particle aggregation. Administration of microneedles coated with trehalose-stabilized influenza vaccine yielded high serum IgG antibody titers even after 1 month storage, and all animals survived with minimal weight loss after lethal challenge infection. Conclusions: Inactivated influenza virus vaccine coated on microneedles with trehalose significantly improved the HA activity as well as in vivo immunogenicity of the vaccine after an extended time of storage.

AB - Purpose: This study sought to determine the effects of microneedle coating formulation, drying time and storage time on antigen stability and in vivo immunogenicity of influenza microneedle vaccines. Methods: The stability of inactivated influenza virus vaccine was monitored by hemagglutination (HA) activity and virus particle aggregation as a function of storage time and temperature with or without trehalose. In vivo immunogenicity of inactivated influenza vaccines coated onto microneedles was determined in mice by virus-specific antibody titers and survival rates. Results: In the absence of trehalose, HA activity decreased below 10% and to almost zero after 1 h and 1 month of drying, respectively. Addition of trehalose maintained HA activity above 60% after drying and above 20% after 1 month storage at 25°C. Loss of HA activity generally correlated with increased virus particle aggregation. Administration of microneedles coated with trehalose-stabilized influenza vaccine yielded high serum IgG antibody titers even after 1 month storage, and all animals survived with minimal weight loss after lethal challenge infection. Conclusions: Inactivated influenza virus vaccine coated on microneedles with trehalose significantly improved the HA activity as well as in vivo immunogenicity of the vaccine after an extended time of storage.

KW - inactivated virus vaccine

KW - influenza virus

KW - long-term stability

KW - microneedle

KW - trehalose

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C2 - 20387097

AN - SCOPUS:78651225461

SN - 0724-8741

VL - 28

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JO - Pharmaceutical Research

JF - Pharmaceutical Research

IS - 1

ER -

Stability kinetics of influenza vaccine coated onto microneedles during drying and storage

Abstract

Bibliographical note

UN SDGs

Keywords

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