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Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
Published on: May 6, 2015
Mucosal adenovirus-vectored vaccine for measles
Liubov M Lobanova1, Tayyba T Baig, Suresh K Tikoo
1Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, SK, S7N 5E3 Canada.
Abstract:
Several problems associated with the available anti-measles vaccine emphasize the need for a single shot anti-measles vaccine which is efficacious by mucosal route of administration and functional in the presence of anti-measles neutralizing antibodies. To achieve these goals, we constructed two recombinant human adenoviruses (collectively designated Ad-F/H) carrying genes for measles virus (MV) fusion (F) and haemagglutinin (H) proteins. Single intranasal or intramuscular vaccination of mice and cotton rats with Ad-F/H elicited high MV-specific serum neutralizing-antibody titers. Furthermore, bronchoalveolar lavage samples from mice vaccinated intranasally with Ad-F/H showed a 100-fold increase in MV-specific IgA titers compared with intramuscularly vaccinated mice. Moreover, Ad-F/H vaccine administered intranasally, but not intramuscularly, completely protected challenged cotton rats from MV replication in the lungs.
Insights
A new single-shot measles vaccine (Ad-F/H) delivered intranasally effectively generates measles virus (MV)-specific antibodies and protects against MV replication, even in the presence of pre-existing antibodies.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- Existing measles vaccines face challenges, necessitating improved single-shot alternatives.
- A need exists for a measles vaccine effective via mucosal administration and functional despite pre-existing neutralizing antibodies.
Purpose of the Study:
- To develop a novel single-shot anti-measles vaccine.
- To evaluate the efficacy of a recombinant adenovirus-vectored vaccine (Ad-F/H) administered via mucosal (intranasal) and intramuscular routes.
- To assess vaccine functionality in the presence of anti-measles neutralizing antibodies.
Main Methods:
- Construction of two recombinant human adenoviruses (Ad-F/H) encoding measles virus (MV) fusion (F) and hemagglutinin (H) proteins.
- Vaccination of mice and cotton rats via intranasal or intramuscular routes.
- Measurement of MV-specific serum neutralizing antibodies and IgA titers.
- Challenge studies to assess protection against MV replication in lungs.
Main Results:
- Intranasal or intramuscular Ad-F/H vaccination induced high MV-specific serum neutralizing-antibody titers in mice and cotton rats.
- Intranasal vaccination led to a 100-fold increase in MV-specific IgA titers in mice compared to intramuscular vaccination.
- Intranasal Ad-F/H administration completely protected cotton rats from MV lung replication, while intramuscular administration did not.
Conclusions:
- The Ad-F/H vaccine is a promising candidate for a single-shot measles vaccine.
- Intranasal administration elicits robust mucosal immunity (IgA) and superior protection against MV replication.
- This vaccine strategy shows potential for overcoming challenges associated with current measles vaccines.
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