RTC STOPINFECTIONS

Abstract:

The spread of bacterial infections resistant to antibiotics is one of the big threats of public health. Mortality,

morbidity-, and costs-associated to antibiotic-resistant infections are increasing significantly every year. By 2050 infections would kill more than cancer. Prevention by vaccination of high-risk populations is an urgently needed measure. However, it is not easy to implement because of 2 main barriers. One of them is the technical difficulty of developing vaccines able to protect against bacterial pathogens. And the other barrier is business-related, specifically the difficulty of introducing new vaccines into healthcare systems, which are familiar to the current economy of antibiotics.

Vaxdyn, Laboratorios Reig-Jofre and Leitat -partners in this project- have been working together in development of a technological platform able to deliver safe and efficacious vaccines against antibiotic-resistant bacteria. The platform is based on an invention patented by Vaxdyn and uses an LPS-null strain of Acinetobacter baumannii, inactivated, for raising a protective immune response in vaccinated subjects. The first vaccine candidate was against A. baumannii, pathogen at the very top of the list of urgent priorities of the WHO. We received funds from the RETOS-COLABORACION 2016 call for development of this first candidate, Acinetovax. The milestones achieved attracted international attention and recently the international private organization Carb-X, formed by The Bill & Melinda Gates Foundation and The Wellcome Trust of the UK, among other organizations, has agreed to fund Vaxdyn’s technological platform with one condition: that the platform is used for development of a trivalent vaccine to protect not only against A. baumannii but also against the bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae, the other 2 pathogens at the top of the list of the WHO, after a proposal made by Vaxdyn to develop this multivalent candidate, called KAPAVAX. The milestones achieved before showed that our platform is able to overcome the technological barrier, but according to the experts of Carb-X, only KAPAVAX, the trivalent vaccine, will be well accepted by healthcare programs, especially those coping with populations with chronic respiratory problems.

Therefore, in this RETOS-COLABORACIÓN 2019 call, we apply for funds needed for complementing the funds obtained from the private Carb-X organization, based on The Boston University, for development of the first vaccine candidate for prevention of infections caused by the 3 pathogens considered the top priority for the WHO.

In the first year (milestone 1) the R&D of Vaxdyn will show efficacy of KAPAVAX in collaboration with the National Microbiology Center of the Institutes of Health Carlos III (CNM-ISCIII), in animal models selected in agreement with Carb-X to be relevant for future clinical applications of the vaccine. Laboratorios Reig-Jofre (RJ) will show viability of manufacturing and will do research in collaboration with Centro Tecnológico Leitat to develop the analytical methods needed for manufacturing.

In the second year (milestone 2), Vaxdyn and CNM-ISCIII will complete the preclinical package by incorporation of R&D about reactogenicity and immunogenicity in rabbits. RJ will deliver the final manufacturing protocol and stability studies, and in collaboration with Leitat, will deliver the final analytical methods for control of manufacturing and characterization of the product.

In the third year (milestone 3), the toxicity studies under GLP conditions will be completed with participation of Vaxdyn and CNM-ISCIII. RJ will deliver the GMP-batch for clinical trials, and Leitat will complete development of a multiplex biosensor able to measure the immune response against the 3 target pathogens. At the end of the project, the consortium will ask to the European Medicines Agency for the permit to begin the clinical Phase I in humans.

The support from the Carb-X program has been secured until completion of the Phase I trial, which is a key business milestone to license-out the vaccine to one of the big pharmaceuticals companies already interested, approximately 1-1.5 years after completion of this project.

Project Budget: 852.774,41€

LEITAT Budget: 232.749,31€

Financial Framework: RTC

Contract number: RTC2019-007058-1

Start Date: 01/01/2020

End Date: 31/12/2022

Contact Manager: Iván Ortiz

Partners: (Vaxdyn Coordinator)