Induction of protective immunity against H1N1 influenza A(H1N1)pdm09 with spray-dried and electron-beam sterilised vaccines in non-human primates

Regina Scherließ; Ankur Ajmera; Michael Dennis; Miles Carroll; Jens Altrichter; Nigel Silman; Martin Scholz; Kristina Kemter; Anthony C. Marriott

doi:10.1016/j.vaccine.2014.01.077

Induction of protective immunity against H1N1 influenza A(H1N1)pdm09 with spray-dried and electron-beam sterilised vaccines in non-human primates

Regina Scherließ
, Ankur Ajmera
, Michael Dennis
, Miles Carroll
, Jens Altrichter
, Nigel Silman
, Martin Scholz^*
, Kristina Kemter
, Anthony C. Marriott

^*Corresponding author for this work

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

22 Citations (Scopus)

Abstract

Currently, the need for cooled storage and the impossibility of terminal sterilisation are major drawbacks in vaccine manufacturing and distribution. To overcome current restrictions a preclinical safety and efficacy study was conducted to evaluate new influenza A vaccine formulations regarding thermal resistance, resistance against irradiation-mediated damage and storage stability. We evaluated the efficacy of novel antigen stabilizing and protecting solutions (SPS) to protect influenza A(H1N1)pdm09 split virus antigen under experimental conditions in vitro and in vivo.Original or SPS re-buffered vaccine (Pandemrix) was spray-dried and terminally sterilised by irradiation with 25. kGy (e-beam). Antigen integrity was monitored by SDS-PAGE, dynamic light scattering, size exclusion chromatography and functional haemagglutination assays. In vitro screening experiments revealed a number of highly stable compositions containing glycyrrhizinic acid (GA) and/or chitosan. The most stable composition was selected for storage tests and in vivo assessment of seroconversion in non-human primates (Macaca fascicularis) using a prime-boost strategy. Redispersed formulations with original adjuvant were administered intramuscularly.Storage data revealed high stability of protected vaccines at 4. °C and 25. °C, 60% relative humidity, for at least three months. Animals receiving original Pandemrix exhibited expected levels of seroconversion after 21 days (prime) and 48 days (boost) as assessed by haemagglutination inhibition and microneutralisation assays. Animals vaccinated with spray-dried and irradiated Pandemrix failed to exhibit seroconversion after 21 days whereas spray-dried and irradiated, SPS-protected vaccines elicited similar seroconversion levels to those vaccinated with original Pandemrix. Boost immunisation with SPS-protected vaccine resulted in a strong increase in seroconversion but had only minor effects in animals treated with non SPS-protected vaccine.In conclusion, utilising the SPS formulation technology, spray-drying and terminal sterilisation of influenza A(H1N1)pdm09 split virus vaccine is feasible. Findings indicate the potential utility of such formulated vaccines e.g. for needle-free vaccination routes and delivery to countries with uncertain cold chain facilities.

Original language	English
Pages (from-to)	2231-2240
Number of pages	10
Journal	Vaccine
Volume	32
Issue number	19
DOIs	https://doi.org/10.1016/j.vaccine.2014.01.077
Publication status	Published - 17 Apr 2014

Bibliographical note

Funding Information:
This work was supported by the German “ Bundesministerium für Wirtschaft ” (ZIM-project KF2788002FRO). We thank the government of the state Brandenburg for providing us with Pandemrix. For excellent technical assistance we thank Simone Knappmann, Karin Heller and Sabine Kietz.

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Dry powder vaccine
Excipients
Irradiation
Stabilising and protecting solution (SPS)
Thermal stability
Viruses

Access to Document

10.1016/j.vaccine.2014.01.077

Cite this

@article{a65db087dd754984967c5573a84c1787,

title = "Induction of protective immunity against H1N1 influenza A(H1N1)pdm09 with spray-dried and electron-beam sterilised vaccines in non-human primates",

abstract = "Currently, the need for cooled storage and the impossibility of terminal sterilisation are major drawbacks in vaccine manufacturing and distribution. To overcome current restrictions a preclinical safety and efficacy study was conducted to evaluate new influenza A vaccine formulations regarding thermal resistance, resistance against irradiation-mediated damage and storage stability. We evaluated the efficacy of novel antigen stabilizing and protecting solutions (SPS) to protect influenza A(H1N1)pdm09 split virus antigen under experimental conditions in vitro and in vivo.Original or SPS re-buffered vaccine (Pandemrix) was spray-dried and terminally sterilised by irradiation with 25. kGy (e-beam). Antigen integrity was monitored by SDS-PAGE, dynamic light scattering, size exclusion chromatography and functional haemagglutination assays. In vitro screening experiments revealed a number of highly stable compositions containing glycyrrhizinic acid (GA) and/or chitosan. The most stable composition was selected for storage tests and in vivo assessment of seroconversion in non-human primates (Macaca fascicularis) using a prime-boost strategy. Redispersed formulations with original adjuvant were administered intramuscularly.Storage data revealed high stability of protected vaccines at 4. °C and 25. °C, 60\% relative humidity, for at least three months. Animals receiving original Pandemrix exhibited expected levels of seroconversion after 21 days (prime) and 48 days (boost) as assessed by haemagglutination inhibition and microneutralisation assays. Animals vaccinated with spray-dried and irradiated Pandemrix failed to exhibit seroconversion after 21 days whereas spray-dried and irradiated, SPS-protected vaccines elicited similar seroconversion levels to those vaccinated with original Pandemrix. Boost immunisation with SPS-protected vaccine resulted in a strong increase in seroconversion but had only minor effects in animals treated with non SPS-protected vaccine.In conclusion, utilising the SPS formulation technology, spray-drying and terminal sterilisation of influenza A(H1N1)pdm09 split virus vaccine is feasible. Findings indicate the potential utility of such formulated vaccines e.g. for needle-free vaccination routes and delivery to countries with uncertain cold chain facilities.",

keywords = "Dry powder vaccine, Excipients, Irradiation, Stabilising and protecting solution (SPS), Thermal stability, Viruses",

author = "Regina Scherlie{\ss} and Ankur Ajmera and Michael Dennis and Miles Carroll and Jens Altrichter and Nigel Silman and Martin Scholz and Kristina Kemter and Marriott, \{Anthony C.\}",

note = "Funding Information: This work was supported by the German {\textquotedblleft} Bundesministerium f{\"u}r Wirtschaft {\textquotedblright} (ZIM-project KF2788002FRO). We thank the government of the state Brandenburg for providing us with Pandemrix. For excellent technical assistance we thank Simone Knappmann, Karin Heller and Sabine Kietz.",

year = "2014",

month = apr,

day = "17",

doi = "10.1016/j.vaccine.2014.01.077",

language = "English",

volume = "32",

pages = "2231--2240",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier Ltd.",

number = "19",

}

TY - JOUR

T1 - Induction of protective immunity against H1N1 influenza A(H1N1)pdm09 with spray-dried and electron-beam sterilised vaccines in non-human primates

AU - Scherließ, Regina

AU - Ajmera, Ankur

AU - Dennis, Michael

AU - Carroll, Miles

AU - Altrichter, Jens

AU - Silman, Nigel

AU - Scholz, Martin

AU - Kemter, Kristina

AU - Marriott, Anthony C.

N1 - Funding Information: This work was supported by the German “ Bundesministerium für Wirtschaft ” (ZIM-project KF2788002FRO). We thank the government of the state Brandenburg for providing us with Pandemrix. For excellent technical assistance we thank Simone Knappmann, Karin Heller and Sabine Kietz.

PY - 2014/4/17

Y1 - 2014/4/17

N2 - Currently, the need for cooled storage and the impossibility of terminal sterilisation are major drawbacks in vaccine manufacturing and distribution. To overcome current restrictions a preclinical safety and efficacy study was conducted to evaluate new influenza A vaccine formulations regarding thermal resistance, resistance against irradiation-mediated damage and storage stability. We evaluated the efficacy of novel antigen stabilizing and protecting solutions (SPS) to protect influenza A(H1N1)pdm09 split virus antigen under experimental conditions in vitro and in vivo.Original or SPS re-buffered vaccine (Pandemrix) was spray-dried and terminally sterilised by irradiation with 25. kGy (e-beam). Antigen integrity was monitored by SDS-PAGE, dynamic light scattering, size exclusion chromatography and functional haemagglutination assays. In vitro screening experiments revealed a number of highly stable compositions containing glycyrrhizinic acid (GA) and/or chitosan. The most stable composition was selected for storage tests and in vivo assessment of seroconversion in non-human primates (Macaca fascicularis) using a prime-boost strategy. Redispersed formulations with original adjuvant were administered intramuscularly.Storage data revealed high stability of protected vaccines at 4. °C and 25. °C, 60% relative humidity, for at least three months. Animals receiving original Pandemrix exhibited expected levels of seroconversion after 21 days (prime) and 48 days (boost) as assessed by haemagglutination inhibition and microneutralisation assays. Animals vaccinated with spray-dried and irradiated Pandemrix failed to exhibit seroconversion after 21 days whereas spray-dried and irradiated, SPS-protected vaccines elicited similar seroconversion levels to those vaccinated with original Pandemrix. Boost immunisation with SPS-protected vaccine resulted in a strong increase in seroconversion but had only minor effects in animals treated with non SPS-protected vaccine.In conclusion, utilising the SPS formulation technology, spray-drying and terminal sterilisation of influenza A(H1N1)pdm09 split virus vaccine is feasible. Findings indicate the potential utility of such formulated vaccines e.g. for needle-free vaccination routes and delivery to countries with uncertain cold chain facilities.

AB - Currently, the need for cooled storage and the impossibility of terminal sterilisation are major drawbacks in vaccine manufacturing and distribution. To overcome current restrictions a preclinical safety and efficacy study was conducted to evaluate new influenza A vaccine formulations regarding thermal resistance, resistance against irradiation-mediated damage and storage stability. We evaluated the efficacy of novel antigen stabilizing and protecting solutions (SPS) to protect influenza A(H1N1)pdm09 split virus antigen under experimental conditions in vitro and in vivo.Original or SPS re-buffered vaccine (Pandemrix) was spray-dried and terminally sterilised by irradiation with 25. kGy (e-beam). Antigen integrity was monitored by SDS-PAGE, dynamic light scattering, size exclusion chromatography and functional haemagglutination assays. In vitro screening experiments revealed a number of highly stable compositions containing glycyrrhizinic acid (GA) and/or chitosan. The most stable composition was selected for storage tests and in vivo assessment of seroconversion in non-human primates (Macaca fascicularis) using a prime-boost strategy. Redispersed formulations with original adjuvant were administered intramuscularly.Storage data revealed high stability of protected vaccines at 4. °C and 25. °C, 60% relative humidity, for at least three months. Animals receiving original Pandemrix exhibited expected levels of seroconversion after 21 days (prime) and 48 days (boost) as assessed by haemagglutination inhibition and microneutralisation assays. Animals vaccinated with spray-dried and irradiated Pandemrix failed to exhibit seroconversion after 21 days whereas spray-dried and irradiated, SPS-protected vaccines elicited similar seroconversion levels to those vaccinated with original Pandemrix. Boost immunisation with SPS-protected vaccine resulted in a strong increase in seroconversion but had only minor effects in animals treated with non SPS-protected vaccine.In conclusion, utilising the SPS formulation technology, spray-drying and terminal sterilisation of influenza A(H1N1)pdm09 split virus vaccine is feasible. Findings indicate the potential utility of such formulated vaccines e.g. for needle-free vaccination routes and delivery to countries with uncertain cold chain facilities.

KW - Dry powder vaccine

KW - Excipients

KW - Irradiation

KW - Stabilising and protecting solution (SPS)

KW - Thermal stability

KW - Viruses

UR - https://www.scopus.com/pages/publications/84897109251

U2 - 10.1016/j.vaccine.2014.01.077

DO - 10.1016/j.vaccine.2014.01.077

M3 - Article

C2 - 24631078

AN - SCOPUS:84897109251

SN - 0264-410X

VL - 32

SP - 2231

EP - 2240

JO - Vaccine

JF - Vaccine

IS - 19

ER -

Induction of protective immunity against H1N1 influenza A(H1N1)pdm09 with spray-dried and electron-beam sterilised vaccines in non-human primates

Abstract

Bibliographical note

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this