- Prevention Vaccine: Malaria, HIV-1, Dengue Virus
According to the World Health Organization, the global incidence of selected infectious diseases is estimated to be over 250 million annually, resulting in 16% of global deaths each year. Despite the robust pipeline, there are high unmet needs in the infectious diseases market. In particular, indications such as Malaria, HIV and Dengue fever have high demand for the development of a first vaccine.
Malaria remains one of the world’s most devastating infectious tropical diseases. It is caused by parasites of the plasmodium genus with transmission occurring from the bite of an infected mosquito to humans, resulting in high fevers, shaking chills, flu-like symptoms and anemia. After infection, the parasites (sporozoites) travel through the bloodstream to the liver, where they mature and are released as merozoites. The merozoites enter the bloodstream where they infect and multiply in red blood cells. The first symptoms usually appear 10 days to 4 weeks after infection and occur in cycles of 48 to 72 hours. Plasmodium falciparum (P. falciparum) is the most virulent strain, responsible for most malaria-associated deaths .
In total, an estimated 3.3 billion people – both civilian and military — are at risk for malarial infection worldwide . According to the World Health Organization (WHO) and the Global Malaria Action Plan, malaria was estimated to cause 198 million clinical cases and 584,000 deaths in 2013 [1, 3]. The most vulnerable populations consist of those with little or no immunity against the disease such as young children, pregnant women and travelers [1, 3]. The impact of malaria in endemic nations is so widespread that malaria-endemic nations face an economic growth penalty by up to 1.3% annually, stemming from lost worker productivity, suboptimal agricultural growth, discouragement in foreign investment and tourism, and impairment in childhood learning; all of these have been estimated to impact their Gross Domestic Product (GDP) by 5%-6%, chronically impeding these nations’ abilities to flourish [4, 5].
Protection against malarial infection has primarily been achieved through personal protective measures, vector control, and chemoprophylaxis. While the short-term protection and treatment rates provided by chemoprophylactics and ACTs can be effective, the emergence of drug-resistant strains to the drugs are pressing the need for more effective, durable measures such as vaccines.
As the malaria parasite has a complex life cycle with expressed in multiple stages in humans and mosquitoes, vaccine development has been challenging. The ideal malaria vaccine would induce sterile immunity by blocking early stage transmission from mosquitoes to humans. Utilizing i-αVLP platform technology, we have developed VLPM01, a pre-erythrocytic vaccine that targets the CSP antigen of P. falciparum sporozoites. VLPM-01 has shown very potent efficacy in pre-clinical studies and is expected to enter into Phase I clinical trial in 1H of 2016.
Dengue is a mosquito-borne tropical disease caused by the dengue virus. According to the World Health Organization, it is the most rapidly spreading viral disease with an estimated 50-100 million dengue infections occurring each year and 3 billion people living in dengue epidemic countries. The number of countries reporting the disease has dramatically increased and over 100 new incidents have recently been reported in non-tropical countries such as Japan. There are no approved therapies to treat dengue and prevention is currently limited to vector control measures while a few vaccines are currently being developed.
Dengue is caused by four closely related viruses, the Dengue viruses 1-4. Infection by one of the four dengue virus types has been shown to offer protection against the same type of dengue virus re-infection, but not against an infection by other types. Moreover, secondary infection by another type of virus seems to increase the severity disease. Due to these complexities, a vaccine providing long-term protection against all four virus types is needed.
At VLP Therapeutics, we have successfully created a VLP for all four types, and are currently conducting animal proof of concept studies.