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December 25, 2012

Progress to Universal Flu Vaccines

Every year, between 250,000 and 500,000 people of all ages die worldwide after getting seasonal flu, partly because few people are vaccinated for it. Flu comes back every year because when you catch it or are vaccinated, your immune system is only trained to identify the flu's large surface proteins. These proteins change from year to year, allowing flu to strike again if you haven't had an updated vaccine.

Most attempts for universal flu vaccines are designed to make us produce antibodies, aimed not at flu's surface proteins, but at internal proteins that are the same in all flu viruses.

Researchers have equipped the smallpox vaccine virus used in the smallpox vaccine with two proteins common to all flu viruses. They reported that this vaccine prevented symptoms in some people experimentally infected with flu, and those that did get sick had milder symptoms.

Vaccines tested in chickens provided a strong T-cells response and less of the virus was passed on.

Combining these vaccines that boost t-cells with the classic vaccines that create antibodies could be more than the sum of its parts. In chickens, for example, antibodies could knock out the main virus, while T-cells mop up the variants that evade the antibodies and allow the virus to keep spreading - and evolving. "We could finally get vaccines that stop viral spread completely," says Butter.



Current vaccines targeting surface proteins can drive antigenic variation resulting either in the emergence of more highly pathogenic viruses or of antigenically distinct viruses that escape control by vaccination and thereby persist in the host population. Influenza vaccines typically target the highly mutable surface proteins and do not provide protection against heterologous challenge. Vaccines which induce immune responses against conserved influenza epitopes may confer protection against heterologous challenge. We report here the results of vaccination with recombinant modified Vaccinia virus Ankara (MVA) and Adenovirus (Ad) expressing a fusion construct of nucleoprotein and matrix protein (NP + M1). Prime and boost vaccination regimes were trialled in different ages of chicken and were found to be safe and immunogenic. Interferon-γ (IFN-γ) ELISpot was used to assess the cellular immune response post secondary vaccination. In ovo Ad prime followed by a 4 week post hatch MVA boost was identified as the most immunogenic regime in one outbred and two inbred lines of chicken. Following vaccination, one inbred line (C15I) was challenged with low pathogenic avian influenza (LPAI) H7N7 (A/Turkey/England/1977). Birds receiving a primary vaccination with Ad-NP + M1 and a secondary vaccination with MVA-NP + M1 exhibited reduced cloacal shedding as measured by plaque assay at 7 days post infection compared with birds vaccinated with recombinant viruses containing irrelevant antigen. This preliminary indication of efficacy demonstrates proof of concept in birds; induction of T cell responses in chickens by viral vectors containing internal influenza antigens may be a productive strategy for the development of vaccines to induce heterologous protection against influenza in poultry.

SOURCES - New Scientist, Oxford Journals, Science Direct

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