Forsøksdyr: Development of a trimeric HA influenza vaccine and a broadly protecting vaccine against all subtypes of influenza

Godkjenningsdato 10.08.2018

Godkjenningsperiode 10.08.2018-09.08.2022

Seasonal influenza causes severe illness and death worldwide, and can affect people in any age group. This infectious disease is even more deadly during unexpected pandemics. Because outer proteins (e.g.HA) on the virus are prone to continuous mutations, our immune system does not always recognize the influenza viruses even when previously exposed to an earlier variant. The most effective measure to prevent disease is vaccination.
Influenza vaccines are produced primarily in chicken eggs. This procedure is time consuming and inefficient and involves making an educated guess almost a year in advance as to which strain of influenzas are most likely to occur next season.
Influenza viruses are constantly evolving due to antigenic drift. A radical change in the virus is likely to cause a pandemic as we will have no immunity towards the virus, and this makes it very necessary to be able to produce an effective vaccine in weeks and not months.

Our group has developed a new rapidly-produced influenza vaccine platform, where targeting virus antigens to antigen presenting cells (APC) of the immune system strongly enhances the immune response towards influenza.
Vaccines carrying two identical hemagglutinins (HA) were found to induce production of specific HA antibodies and protected mice against influenza infection. Our intention with this application is to further enhance this protective effect by designing a vaccine that will allow HA to act as trimer, as this is its natural structure. In addition, we want to induce a broad protection against influenza by utilizing the conserved Stem area of the HA.
Although all vaccines are tested in vitro for function and structure, no methods provide necessary information of immunogenicity without using animal models. For this purpose 475 mice will be vaccinated and the formation of immune responses examined. To minimize discomfort, mice are anesthetized before vaccination and electroporation, and placed on a heating pad and after wrapped in blankets to avoid hypothermia. Blood sampling is performed maximum once a week and in accordance with the guidelines. For an influenza vaccine it is also important to investigate whether it can actually protect against influenza virus, so the mice will be infected with different strains of influenza to assess how wide protection we can induce. Very little adverse effects are expected in the animals. For the most vulnerable groups (negative controls) we expect to see a weight loss associated with influenza infection. When weight loss exceeds 20%, the mice will be euthanized. This endpoint is considered humane as it will prevent severe pain and discomfort for the animals. Results from previous experiments have shown us how to utilize as few animals as possible, but still be statistically significant.