Midtveisevaluering - Shahinul Islam

Abstrakt

Influenza infection occurs each year, often recognized as seasonal epidemics causing severe illness worldwide and resulting 500 000 deaths globally. Although the burden of hospitalization is highest in very young children and the elderly, influenza infects all age groups. Vaccination is still the main method of influenza prophylaxis but the vaccine needs to be reformulated annually due to the ability of the virus to escape existing immunity. The LAIV (live attenuated influenza vaccine) was first licensed in 2012 in Europe for children (2-17 years old). LAIV is safe and convenient for young children, administered as a nasal spray, inducing both humoral and cellular immune responses. Trivalent LAIV (LAIV3) has been reported to have a higher efficacy in young children, providing better protection against mismatched strains.

Vaccine-induced antibodies directed against the main surface glycoproteins of the influenza virus, haemagglutinin (HA) and neuraminidase (NA). The HA has two domains; the globular head and the stalk domain. If a virus has a highly divergent HA head from a previously circulating strain, such as the 2009 pandemic virus or avian H5N1, the antibody response can be boosted to the more conserved but less immunogenic stalk. Antibodies directed against the HA stalk are broadly neutralizing, recognizing divergent and heterosubtypic strains. Therefore, we are working on the hypothesis that LAIV can be promising priming vaccine for young children inducing an antibody response similar to natural infection.

The first study was the part of a large clinical trial conducted in Haukeland Hospital after ethical and regulatory approval. Plasma samples were collected from 20 children and 20 adults pre- and post-LAIV3 vaccination (up to a year) and analysed using serological assays. We found that LAIV3 elicited H3-head and low level of H1 stalk specific antibody responses in children. Heterosubtypic H5 and H7 full-length HA specific antibodies were not boosted in either children or adults. In an ongoing project with Norwegian Institute of Public health, we are studying patients admitted to hospital with influenza in Norway, during the 2015-16 season. Primary screening by the gold standard serological assay; Haemagglutinin Inhibition (HI) assay confirmed H1N1 infection in 2015-16 seasons.

During my research so far, we have dissected the HA head and stalk-specific antibody responses, as well as the influenza virus specific neutralizing antibodies, to the homologous vaccine (H1N1 and H3N2) and heterologous avian (H5N1 and H7N9) viruses after intranasal seasonal LAIV3 vaccination in children and adults. In ongoing work the antibody response is being dissected in infected patients.