Pulmonary delivery of influenza vaccine formulations in cotton rats: site of deposition plays a minor role in the protective efficacy against clinical isolate of H1N1pdm virus
Administration of influenza vaccines to the lungs could be an attractive alternative to conventional parenteral administration. In this study, we investigated the deposition site of pulmonary delivered liquid and powder influenza vaccine formulations and its relation to their immunogenicity and prot...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2018-01-01
|
| Series: | Drug Delivery |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/10717544.2018.1435748 |
| _version_ | 1819225694579720192 |
|---|---|
| author | Yoshita Bhide Jasmine Tomar Wei Dong Jacqueline de Vries-Idema Henderik W. Frijlink Anke Huckriede Wouter L. J. Hinrichs |
| author_facet | Yoshita Bhide Jasmine Tomar Wei Dong Jacqueline de Vries-Idema Henderik W. Frijlink Anke Huckriede Wouter L. J. Hinrichs |
| author_sort | Yoshita Bhide |
| collection | DOAJ |
| description | Administration of influenza vaccines to the lungs could be an attractive alternative to conventional parenteral administration. In this study, we investigated the deposition site of pulmonary delivered liquid and powder influenza vaccine formulations and its relation to their immunogenicity and protective efficacy. In vivo deposition studies in cotton rats revealed that, the powder formulation was mainly deposited in the trachea ( ∼ 65%) whereas the liquid was homogenously distributed throughout the lungs ( ∼ 96%). In addition, only 60% of the antigen in the powder formulation was deposited in the respiratory tract with respect to the liquid formulation. Immunogenicity studies showed that pulmonary delivered liquid and powder influenza formulations induced robust systemic and mucosal immune responses (significantly higher by liquids than by powders). When challenged with a clinical isolate of homologous H1N1pdm virus, all animals pulmonary administered with placebo had detectable virus in their lungs one day post challenge. In contrast, none of the vaccinated animals had detectable lung virus titers, except for two out of eight animals from the powder immunized group. Also, pulmonary vaccinated animals showed no or little signs of infection like increase in breathing frequency or weight loss upon challenge as compared to animals from the negative control group. In conclusion, immune responses induced by liquid formulation were significantly higher than responses induced by powder formulation, but the overall protective efficacy of both formulations was comparable. Thus, pulmonary immunization is capable of inducing protective immunity and the site of antigen deposition seems to be of minor relevance in inducing protection. |
| first_indexed | 2024-12-23T10:13:40Z |
| format | Article |
| id | doaj.art-39740d4132234a51bdd87001bc4475a1 |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-12-23T10:13:40Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-39740d4132234a51bdd87001bc4475a12022-12-21T17:50:53ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642018-01-0125153354510.1080/10717544.2018.14357481435748Pulmonary delivery of influenza vaccine formulations in cotton rats: site of deposition plays a minor role in the protective efficacy against clinical isolate of H1N1pdm virusYoshita Bhide0Jasmine Tomar1Wei Dong2Jacqueline de Vries-Idema3Henderik W. Frijlink4Anke Huckriede5Wouter L. J. Hinrichs6University of Groningen, University Medical Center GroningenUniversity of GroningenUniversity of Groningen, University Medical Center GroningenUniversity of Groningen, University Medical Center GroningenUniversity of GroningenUniversity of Groningen, University Medical Center GroningenUniversity of GroningenAdministration of influenza vaccines to the lungs could be an attractive alternative to conventional parenteral administration. In this study, we investigated the deposition site of pulmonary delivered liquid and powder influenza vaccine formulations and its relation to their immunogenicity and protective efficacy. In vivo deposition studies in cotton rats revealed that, the powder formulation was mainly deposited in the trachea ( ∼ 65%) whereas the liquid was homogenously distributed throughout the lungs ( ∼ 96%). In addition, only 60% of the antigen in the powder formulation was deposited in the respiratory tract with respect to the liquid formulation. Immunogenicity studies showed that pulmonary delivered liquid and powder influenza formulations induced robust systemic and mucosal immune responses (significantly higher by liquids than by powders). When challenged with a clinical isolate of homologous H1N1pdm virus, all animals pulmonary administered with placebo had detectable virus in their lungs one day post challenge. In contrast, none of the vaccinated animals had detectable lung virus titers, except for two out of eight animals from the powder immunized group. Also, pulmonary vaccinated animals showed no or little signs of infection like increase in breathing frequency or weight loss upon challenge as compared to animals from the negative control group. In conclusion, immune responses induced by liquid formulation were significantly higher than responses induced by powder formulation, but the overall protective efficacy of both formulations was comparable. Thus, pulmonary immunization is capable of inducing protective immunity and the site of antigen deposition seems to be of minor relevance in inducing protection.http://dx.doi.org/10.1080/10717544.2018.1435748whole inactivated influenza virus vaccineinhalationdepositionimmunogenicityprotection |
| spellingShingle | Yoshita Bhide Jasmine Tomar Wei Dong Jacqueline de Vries-Idema Henderik W. Frijlink Anke Huckriede Wouter L. J. Hinrichs Pulmonary delivery of influenza vaccine formulations in cotton rats: site of deposition plays a minor role in the protective efficacy against clinical isolate of H1N1pdm virus Drug Delivery whole inactivated influenza virus vaccine inhalation deposition immunogenicity protection |
| title | Pulmonary delivery of influenza vaccine formulations in cotton rats: site of deposition plays a minor role in the protective efficacy against clinical isolate of H1N1pdm virus |
| title_full | Pulmonary delivery of influenza vaccine formulations in cotton rats: site of deposition plays a minor role in the protective efficacy against clinical isolate of H1N1pdm virus |
| title_fullStr | Pulmonary delivery of influenza vaccine formulations in cotton rats: site of deposition plays a minor role in the protective efficacy against clinical isolate of H1N1pdm virus |
| title_full_unstemmed | Pulmonary delivery of influenza vaccine formulations in cotton rats: site of deposition plays a minor role in the protective efficacy against clinical isolate of H1N1pdm virus |
| title_short | Pulmonary delivery of influenza vaccine formulations in cotton rats: site of deposition plays a minor role in the protective efficacy against clinical isolate of H1N1pdm virus |
| title_sort | pulmonary delivery of influenza vaccine formulations in cotton rats site of deposition plays a minor role in the protective efficacy against clinical isolate of h1n1pdm virus |
| topic | whole inactivated influenza virus vaccine inhalation deposition immunogenicity protection |
| url | http://dx.doi.org/10.1080/10717544.2018.1435748 |
| work_keys_str_mv | AT yoshitabhide pulmonarydeliveryofinfluenzavaccineformulationsincottonratssiteofdepositionplaysaminorroleintheprotectiveefficacyagainstclinicalisolateofh1n1pdmvirus AT jasminetomar pulmonarydeliveryofinfluenzavaccineformulationsincottonratssiteofdepositionplaysaminorroleintheprotectiveefficacyagainstclinicalisolateofh1n1pdmvirus AT weidong pulmonarydeliveryofinfluenzavaccineformulationsincottonratssiteofdepositionplaysaminorroleintheprotectiveefficacyagainstclinicalisolateofh1n1pdmvirus AT jacquelinedevriesidema pulmonarydeliveryofinfluenzavaccineformulationsincottonratssiteofdepositionplaysaminorroleintheprotectiveefficacyagainstclinicalisolateofh1n1pdmvirus AT henderikwfrijlink pulmonarydeliveryofinfluenzavaccineformulationsincottonratssiteofdepositionplaysaminorroleintheprotectiveefficacyagainstclinicalisolateofh1n1pdmvirus AT ankehuckriede pulmonarydeliveryofinfluenzavaccineformulationsincottonratssiteofdepositionplaysaminorroleintheprotectiveefficacyagainstclinicalisolateofh1n1pdmvirus AT wouterljhinrichs pulmonarydeliveryofinfluenzavaccineformulationsincottonratssiteofdepositionplaysaminorroleintheprotectiveefficacyagainstclinicalisolateofh1n1pdmvirus |