Research Areas:

Respiratory Viruses

Influenza (flu) is a contagious respiratory disease caused by influenza viruses. It can cause mild to severe illness. Every year over half a million people die of seasonal influenza. Many different influenza viruses are found around the globe and these viruses easily mutate to new virus variants.

In addition, there is the constant threat of a new pandemic influenza virus. A ‘new’ virus that may be formed after recombination between bird-influenza viruses and pig-influenza viruses, and that is able cause serious disease in humans. A scenario similar to the Spanish flu in 1918 which killed over 50 million people.

Ideally, an influenza vaccine would provide protection against a broad spectrum of seasonal influenza, as well as pandemic influenza viruses. However, current influenza vaccines afford only limited protection against seasonal as well as pandemic influenza. Therefore, new and improved vaccine-strategies are required. This involves new vaccine concepts as well as improved vaccine production technologies.

At BPRC we use influenza infection models in monkeys to evaluate the protective capacity of several novel vaccine strategies.

Experimental animal models for universal influenza vaccines

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Non-human primate animal models are important to determine whether novel vaccines against influenza can give a good and broad protection against influenza virus and are safe to use. In order to measure protection it is necessary to experimentally expose animals to influenza virus. This exposure is usually done by giving a large amount of virus in the nose, mouth and directly in the lungs. However, infection in humans is assumed to be mainly caused by exposure to aerosols or droplets that enter the airways either via respiration, inhalation or via contact with contaminated surfaces. To better mimic this typical human way of exposure we studied whether non-human primates could also become infected by virus in aerosols. We saw that indeed animals do become infected, but that the reaction of the body is somewhat different from when the virus is directly injected into the lungs. Infection by aerosols gives lower levels of inflammation and may therefore be more typical of a mild infection in humans. Instead, direct injection in the lungs gives more of an inflammatory response, typical of the more severe infection that develops in some humans. These findings can contribute to using the correct animal model for testing of vaccines for use in humans and better prediction of the effect that a vaccine will have in humans.

 

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Needle-free influenza vaccine protects rhesus macaques against H1N1 influenza

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The production of conventional influenza vaccines is a complicated and time consuming process. By contrast DNA vaccines can be rapidly produced and offers tailor-made flexibility to efficiently counter newly emerging influenza virus strains. However, a drawback of DNA vaccines is their generally low immunogenicity in non-human primates and humans. Norwegian scientists have developed a novel DNA influenza vaccine strategy that induced good immune responses in ferrets and pigs. BPRC evaluated this vaccine in rhesus macaques. The vaccine, a DNA vaccine encoding for a bivalent fusion protein that targets influenza virus hemagglutinin (HA) to Mamu class II molecules, was intradermally administered by pain- and needle-free jet injections. The vaccine induced neutralizing antibodies and antigen-specific T cells and protected against a challenge with influenza virus. This type of needle free DNA vaccination may become an effective way to rapidly and efficiently protect people to emerging seasonal or pandemic influenza virus strains. Read more >

 

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PET-CT

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Severe influenza illness is associated with pathology in the lungs. In 2019 we introduced PET-CT into our influenza research program. PET-CT was used to monitor lung lesions over time, shedding light on disease development. In 2020 we are planning to use PET-CT to test influenza vaccine efficacy.

 

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New in vitro assays

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At BPRC we are constantly developing and optimizing in vitro laboratory assays to analyze the anti-viral immunity. We use these tests to study immune responses after influenza vaccination or infection in monkeys. Influenza virus infection results in formation of antibodies against the virus that can protect against a new infection with the same virus. However, the influenza virus itself can change from season to season and sometimes these antibodies are then no longer protective. We have studied the function of these antibodies in several in vitro assays and saw that at a high concentration they will block the infection either directly or via interaction with other cells of the immune system. However, at a low concentration these antibodies may actually enhance infection. Read more >

 

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PhD student influenza specific antibody responses

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Protection from influenza infection relies on good antibody responses. In collaboration with the Amsterdam Medical Centre we are currently training a PhD student to study the plasticity of antibody producing B-cells. For this project we use in vitro models and blood samples from previously vaccinated rhesus macaques. The results of the project will lead to better understanding of antibodies after influenza-vaccination.

 

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