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Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Recombinant Measles AIK-C Vaccine Strain Expressing Influenza HA Protein
Takashi Ito1, Takuji Kumagai2, Yoshiaki Yamaji1
1Laboratory of Viral Infection II, Kitasato Institute for Life Sciences, Tokyo 108-8641, Japan.
Abstract:
Recombinant measles AIK-C vaccine expressing the hemagglutinin (HA) protein of influenza A/Sapporo/107/2013(H1N1pdm) (MVAIK/PdmHA) was constructed. Measles particle agglutination (PA) and influenza hemagglutinin inhibition (HI) antibodies were induced in cotton rats immunized with MVAIK/PdmHA. Cotton rats immunized with two doses of the HA split vaccine were used as positive controls, and higher HI antibodies were detected 3 weeks after the first dose. Following the challenge of A/California/07/2009(H1N1pdm), higher viral loads (107 TCID50/g) were detected in the lung homogenates of cotton rats immunized with the empty vector (MVAIK) or control groups than those immunized with MVAIK/Pdm HA (103 TCID50/g) or the group immunized with HA split vaccine (105 TCID50/g). Histopathologically, destruction of the alveolar structure, swelling of broncho-epithelial cells, and thickening of the alveolar wall with infiltration of inflammatory cells and HA antigens were detected in lung tissues obtained from non-immunized rats and those immunized with the empty vector after the challenge, but not in those immunized with the HA spilt or MVAIK/PdmHA vaccine. Lower levels of IFN-α, IL-1β, and TNF-α mRNA, and higher levels of IFN-γ mRNA were found in the lung homogenates of the MVAIK/PdmHA group. Higher levels of IFN-γ mRNA were detected in spleen cell culture from the MVAIK/PdmHA group stimulated with UV-inactivated A/California/07/2009(H1N1pdm). In conclusion, the recombinant MVAIK vaccine expressing influenza HA protein induced protective immune responses in cotton rats.
Insights
A novel recombinant measles virus vaccine expressing influenza hemagglutinin (HA) protein successfully induced protective immunity against H1N1 influenza in cotton rats. This vaccine candidate demonstrated reduced viral loads and improved lung tissue health post-challenge.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Influenza A virus poses a significant global health threat, necessitating novel vaccine strategies.
- Measles virus vectors offer a promising platform for developing multivalent vaccines.
- Developing effective vaccines against pandemic influenza strains remains a priority.
Purpose of the Study:
- To construct and evaluate a recombinant measles virus vaccine expressing the hemagglutinin (HA) protein of influenza A/Sapporo/107/2013(H1N1pdm).
- To assess the immunogenicity and protective efficacy of this novel vaccine candidate in a preclinical model.
Main Methods:
- Construction of a recombinant measles AIK-C vaccine (MVAIK/PdmHA) expressing influenza HA protein.
- Immunization of cotton rats with MVAIK/PdmHA, an empty vector (MVAIK), or an influenza HA split vaccine.
- Challenge with A/California/07/2009(H1N1pdm) and assessment of viral loads, histopathology, and cytokine mRNA expression.
Main Results:
- MVAIK/PdmHA induced measles particle agglutination (PA) and influenza hemagglutinin inhibition (HI) antibodies.
- Vaccination with MVAIK/PdmHA significantly reduced viral loads in the lungs compared to control groups after H1N1 challenge.
- Histopathological analysis revealed protection of lung tissue structure in MVAIK/PdmHA-immunized rats.
- The vaccine modulated immune responses, showing lower pro-inflammatory cytokine mRNA (IFN-α, IL-1β, TNF-α) and higher anti-inflammatory cytokine mRNA (IFN-γ) in lung tissues.
Conclusions:
- The recombinant measles virus vaccine expressing influenza HA protein is immunogenic and confers protective immunity against H1N1 influenza in cotton rats.
- This vaccine platform holds potential for developing effective combination vaccines against measles and influenza.
- Further studies are warranted to explore the full potential of this recombinant vaccine strategy.
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