Journal of Vaccines & Vaccination

Development of the intranasal RSV vaccine SynGEM

6^th Euro Global Summit and Expo on Vaccines & Vaccination

August 17-19, 2015 Birmingham, UK

Kees Leenhouts1, Bert Jan Haijema1, Maarten van Roosmalen1, Ivy Widjaja1,2, Alan Rigter1,2, Peter J M Rottier2 and Cornelis A M de Haan2

Posters-Accepted Abstracts: J Vaccines Vaccin

Abstract:

Respiratory syncytial virus (RSV) is an important cause of respiratory tract disease in (naive) young infants, older infants,
the elderly and immune-compromised. Despite the medical need and the market potential, no licensed vaccine is available.
Each of the target populations differs fundamentally with respect to its immune-capabilities and RSV history. It is therefore
the current understanding that different populations present different challenges for vaccine development. An intramuscular
vaccine that elicits high VN titers is now considered the most suitable approach for maternal vaccination of pregnant mothers.
The placental transfer of antibodies to the foetus should protect the naive infant up to the 6 month of live. On the other hand,
a mucosal vaccine that inactivates the virus in the upper respiratory tract (already at the port of entry) may be attractive for
vaccination of other target groups like children older than 6 months as part of a cocooning strategy to protect vulnerable
people (elderly, immune-compromised and naives). In support of the mucosal approach, there is accumulating evidence that
F-specific local S-IgA antibodies secreted in the upper respiratory tract of humans, correlate well with protection. Because of
its ability to induce broadly neutralizing antibodies the RSV F protein is the most attractive antigen. The current view is that
in particular serum antibodies directed against the prefusion form of RSV F belong to the most potent neutralizing antibodies
and the ability to elicit these is a pivotal attribute for a successful RSV vaccine. We studied different variants of F with respect
to their conformation using neutralizing monoclonal antibodies, following the view that F proteins mimicking the meta-stable
prefusion form of F expose a more extensive and relevant epitope repertoire than F proteins corresponding to the postfusion F
structure. Both addition of a trimerization motif and mutation of the furin cleavage sites increased the reactivity of F with the
prefusion-specific D25, with the highest reactivity being observed for F proteins in which both these features were combined.
The RSV vaccine SynGEM based on this prefusion-type F protein was evaluated in several animal models and is currently in
development for clinical trials. Our progress in these areas will be discussed.