Special Project – EU Malaria Fund

SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, is a respiratory Coronavirus that has rapidly spread worldwide to pandemic levels becoming a Public Health Emergency of International Concern. On the 11^th February 2020, the World Health Organization (WHO) announced that the respiratory disease caused by 2019-nCoV had been officially named Covid-19 (Corona Virus Disease 2019). Covid-19 infection has a high death toll especially, but not exclusively, amongst elderly patients with pre-existing comorbidities.

No vaccines, immune therapeutics or effective drugs are currently licensed against Covid-19. Even if a successful solution were found, it is expected that significant time will be needed for large-scale implementation of immunization programs.

Vaccines are a long-term solution against emerging infections. However, in an emergency situation such as the Covid-19 pandemic, monoclonal antibodies are a pivotal tool that can be used for immediate therapy of any patient testing positive for the virus, and to provide immediate protection from infection in high-risk individuals for a number of months.

Antibodies are proteins generated by the immune system. They are one of the host resistance mediators against infection. Antibodies can be used for the treatment of infectious diseases, cancer and autoimmune syndromes.

Monoclonal antibodies (mAbs) are derived from identical host immune cells that originate from a single progenitor B-lymphocyte that recognizes a single molecular structure. Monoclonal antibodies can be manufactured at commercial scale using the appropriate cell-based expression systems. These human-derived proteins are a valuable pharmaceutical remedy to cure and prevent disease.

mAbs are one of the most effective pharmaceutical remedies in modern medicine. Only few of about 100 currently licensed mAbs are for use in the treatment of infectious diseases. However, in the future mAbs are expected to play a key role in curing and preventing infectious diseases especially those caused by emerging pathogens and microbes that exhibit an increasing level of antibiotic resistance.

The MAbCo19 project aims to rapidly deliver a human neutralizing monoclonal antibody as prophylactic and therapeutic tool against Covid-19. Human antibodies have proven to be powerful solution for diseases like HIV, RSV and recently provided the first cure for Ebola.

The project will exploit cutting edge technology, where B-cells from Covid-19 convalescent patients are selected for their ability to produce high-affinity antibodies. The genes encoding these antibodies are cloned in appropriate expression (antibody-production) systems, followed by preclinical evaluation of their protective efficacy and further rational engineering to achieve maximum therapeutic efficiency. MAbCo19 is engineered to have a high virus-neutralizing potency and it will be easily administered via the intramuscular route.

Dr. Rino Rappuoli

Malaria is an acute febrile disease caused by several species of Plasmodium parasites that are transmitted by infected Anopheles mosquitos. Symptoms range from mild to severe depending on the age of the individual and pre-existing immunity. Severe anaemia, respiratory distress, cerebral malaria and multiorgan failure can lead to death.

In recent years there have been about 230 million annual cases of malaria worldwide, leading to over 400.000 deaths. Children aged under 5 years are the most vulnerable group affected by malaria. The WHO African Region is home to more than 90% of cases and deaths. Malaria can also be a predisposing co-morbidity for a number of other infections including fatal bacterial septicamias.

Drug resistance against Plasmodium parasites is widespread and resistance to insecticides posed difficulties to control of the mosquito transmission vectors.
Despite decades of intense research in the field, a protective, effective, and affordable vaccine has yet to be developed.

AchilleS Vaccines aims to move away from traditional approaches and use multidisciplinary, combinatorial, innovative science towards malaria vaccine development. The MalOMVax project will exploit advanced clinical-immunology-guided reverse vaccinology, combined to the fllexible mOMV platform, to deliver antigens able to induce protective immunity against a broad range of Plasmodium parasites. New antigens and epitopes that can be recognized by immune B-cells of “protected” individuals from endemic areas will be identified, prioritized for functional protective activity, further engineered for optimal immunogenicity and displayed on the mOMV platform.

Our approach will maximize the chances of developing a novel mOMV-based malaria vaccine capable of eliciting strong immunity against multiple parasite antigens and providing long-lasting protection. The project will be performed as a collaboration between AchilleS vaccines (Siena, Italy) and the National Institute of Molecular Genetics (Milan, Italy).

These diseases co-exist in many geographical areas, especially in Low and Middle Income Countries (LMIC). Therefore, a single vaccine against all the major Salmonella infections would be highly desirable.

The project, funded by the Wellcome Trust, will use genetically engineered mOMV to target various salmonella-related infections in a single vaccine preparation. The vaccine will have the advantages of efficacy, multivalency, safety and low production cost and will therefore benefit both travelers and those who live in endemic areas.