The overall objective was to manufacture the CyRPA antigen, followed by its incorporation into a novel multi-stage malaria vaccine formulation against Plasmodium falciparum (Pf), based on the influenza virosomes acting as synthetic lipid-based particle carriers. This vaccine contains two virosomes, each with two surface antigens: one with the highly conserved antigens CyRPA & RH5 as recombinant proteins and one virosome with AMA and CSP peptidomimotopes. These virosomes contain the TLR7/8 adjuvant suitable for infants, children and adults. Adjuvants and antigens are physically bound to the same virosome for improving the vaccine safety and tolerance profile. Mice and rabbit immunized with the two combined virosomes developed good antibody levels toward each antigen, capable of binding to the parasite and strongly reducing its infectivity in laboratory tests. Human vaccinated with this malaria vaccine candidate should develop anti-parasite antibodies preventing/controlling red blood cell infection, greatly alleviating symptoms and reducing risk of severe malaria.

The main outcome of this project was the production, fine characterization, and pre-selection of optimal stable adjuvant formulations of near native recombinant trimeric ZEBOV GP protein developed as part of the IMI/EU project PEVIA, and produced using break-through technologies. We identified several formulations that retain the trimeric structure of the GP antigen using physico-chemical analyses done by UNIL. The B and T cell immunogenicity of these formulated GP antigens were compared to the Alum reference adjuvant and Three formulations were shown to generate balanced GP specific antibody and IFNg+ T cells responses using a relevant mouse model and were selected as optimal adjuvants.

The results achieved are patentable, so unfortunately we cannot disseminate them (ongoing process).

The current outbreak of SARS-CoV-2 has demonstrated the need for development of vaccine formats that can rapidly become available for aiding in control of a pandemic. Here, the main aim was to complete the preclinical experiments needed for translation to humans of a novel DNA vaccine against influenza H7N9. This is one of the more likely influenza viruses to cause the next influenza pandemic.
The more specific aim for this project was to evaluate the protective efficacy of the novel vaccine format in ferrets, as these represent the gold-standard model for influenza.
Importantly, we were able to demonstrate that vaccination with the novel DNA vaccine could protect ferrets against a lethal challenge with influenza H7N9. As such, completion of the experiment has enabled progression to a Phase I trial with the novel DNA vaccine.

Leishmaniasis is a globally important but neglected disease spread by the bite of female sand flies.
Approximately 1.5 million new cases are reported annually, with an estimated 1 billion people at risk. A novel vaccine for leishmaniasis, developed by researchers at the University of York, is being tested in leishmaniasis patients in Sudan to see if it can be used to treat patients by stimulating their immune system and replace the need to use toxic drugs. The aim of the current project is to analyze blood samples from these patients to identify what types of immune response are stimulated by the vaccine. The results will help further develop this vaccine, ultimately leading to better treatments for patients.

First production of the adjuvant flagellin has been achieved in bacteria with interesting yield, purity, and biological activity. The GLP-grade batch will be produced in fall 2019 according to the pipeline that was already set up for the first batch in order to start a toxicology study for the H2020 FAIR project (call SC1-BHC-14-2019)  that was recently obtained and that includes the user laboratory and SSI as partners.

PLLAV (plasmid launched live-attenuated vaccine) is a novel vaccine platform technology that combines the assets of both DNA and live-attenuated vaccines (LAV). PLLAV-based vaccines are thermostable and amenable to mass production. Here, we wanted to reach preclinical proof that both PLLAV-YF-ZIK (yellow fever – Zika virus) and LAV YF-ZIK are immunogenic, safe and efficient in non-human primates (NHPs) after completion of our data package in rodent models. Thereto, a group of 6 NHPs each received either the PLLAV or LAV version of this vaccine. In both groups, except for one PLLAV-vaccinated animal, high titers of neutralizing antibodies against ZIKV were elicited with no clear signs of any adverse events. Moreover, animals were protected against challenge with ZIKV as no viral load in serum could be detected.
These data warrant the further development of (PL)LAV YF-ZIKA towards prophylactic use in humans for the prevention of ZIKV infection and Zika congenital syndrome.

Osivax is developing vaccines based on its proprietary technology oligoDOM® triggering powerfully cellular immune response. The most advanced project is a broad-spectrum flu vaccine candidate in phase I. The aim of this project is to finalize the preclinical development of a second-generation universal influenza vaccine candidate, with a broader breadth of protection and an optimized IM immunization strategy, to provide long-term >70% protection from morbidity and mortality caused by all types of A and B influenza viruses. The first step of the project assessed the stability of the vaccine formulated with 5 different adjuvants. Four adjuvanted formulations have been selected for the next step of the project and will be tested and down-selected based on their level of immunogenicity in mice.

The study was successfully performed under high quality standards with clear interpretable results. A solid
proof of concept for the efficacy for Malcisbo’s APP2 glycoconjugate vaccine (intranasal / oral) in
combination with injected Apx toxins was achieved. Also, a superiority compared to a commercial APP
vaccine could be shown. For other variants of Malcisbo’s APP2 glycoconjugate vaccine no significant
increased efficacy could be detected partially due to the animal numbers per group. For future studies, an
increase of animal numbers per group needs to be considered. As a conclusion the Malcisbo’s APP2
glycoconjugate vaccine (intranasal / oral) in combination with injected Apx toxins presents a good vaccine
candidate to be further developed into a pan-APP vaccine. In addition, further development is needed to
improve the efficacy of the injected APP2 glycoconjugate vaccine in combination with the Apx toxins.

Immunogenicity of two fragments of SARS-CoV-2 Spike protein (Subunit A and C) and receptor binding domain (‘RBD’) in combination with a novel, fully synthetic, carbohydrate fatty acid monosulphate ester adjuvant (‘CMS’) was tested in large non-rodent species. All three SARS-CoV-2 antigens gave significant ELISA antibody responses after the first and/or second immunization and titers were significantly higher with CMS than with MF59 or AS03. Further research of the serum samples will include determination of virus neutralizing activity and quantitative and qualitative analyses of antibodies by competitive ELISA with neutralizing and non-neutralizing monoclonal antibodies. We concluded that the two fragments of S protein are immunogenic and that a combination of Subunit C and CMS is an interesting lead for a single-shot COVID19 vaccine.