SynCon® vaccines targeting malaria


Phase I/IIa

  • Malaria preventive

 




malaria stain

Description
Inovio is developing two synthetic multi-antigen DNA vaccines targeting the pre-erythrocytic stage of the malaria parasite Plasmodium falciparum to prevent the onset of malaria symptoms and further inhibit spread of the disease. INO-7105 encodes for four pre-erythrocytic antigens, CSP, TRAP, LSA-1, and CelTOS, and one blood stage antigen, AMA-1. The second vaccine, INO-7103, encodes for pre-erythrocytic malaria antigens CSP and TRAP as well as one blood stage antigen, AMA-1. The vaccines will be delivered with Inovio's intramuscular CELLECTRA ® 5P delivery device.

Development Status
Preclinical studies demonstrated potent T-cell and antibody responses in animal subjects. The PATH Malaria Vaccine Initiative funded and conducted these preclinical studies and indicated their intent to conduct a phase I/IIa study to test INO-7105 and INO-7103 delivered using Inovio’s CELLECTRA 5P electroporation technology in approximately 30 individuals as part of a challenge trial. The study subjects would be given four doses of one of the DNA vaccines prior to being exposed to the malaria parasite through the bites of multiple malaria infected mosquitos. Successful results of this trial could prove these vaccines are capable of inducing an immune response in humans that protects against malaria. Inovio is prepared to advance this program into a clinical trial, but the actual timing of the human study is dependent upon funding from MVI or other funding agencies.

Disease State
Malaria is a disease caused by parasites and is transmitted through the bite of an infected mosquito. The most deadly malaria parasite is Plasmodium falciparum, which undergoes multiple developmental stages during its life cycle. Each stage of development presents different potential target antigens as the parasite passes through the human and mosquito host, making the manufacturing and development of an effective vaccine difficult. According to WHO, there were approximately 207 million cases of malaria in 2012 and an estimated 627,000 deaths. 



Clinical Trials

Clinical Trials

Malaria Vaccines

We completed preclinical studies that demonstrated potent T-cell and antibody responses in animal subjects. The PATH Malaria Vaccine Initiative funded and conducted these preclinical studies and indicated their intent to conduct a phase I/IIa study to test INO-7105 and INO-7103 delivered using Inovio’s CELLECTRA 5P electroporation technology in approximately 30 individuals as part of a challenge trial. Study subjects would be given four doses of one of the DNA vaccines intramuscularly prior to being exposed to the malaria parasites through the bites of multiple malaria infected mosquitos 30 days after the fourth vaccination. Inovio is prepared to advance this program into a clinical trial, but the actual timing of the human study is dependent upon funding from MVI or other funding agencies.

Study Data

Study Data

Malaria Vaccines

Inovio and PATH/MVI tested Inovio’s DNA plasmids targeting multiple malaria parasite antigens in pre-clinical trials. Results from this study indicated that Inovio’s vaccine demonstrated potent robust and long-lasting T cell responses that exhibited the functional ability to kill and eliminate malaria-infected cells in small animals and non-human primates. Inovio also found that its SynCon® vaccine induced CD-8+ "killer T cells" in the liver, which is essential for rapid elimination of liver-stage malaria parasites. These results were published in Infection & Immunity in 2013.

Inovio is prepared to advance this program into a clinical trial, but the actual timing of the human study is dependent upon proper and timely funding from MVI or other funding agencies.

More Information

More Information

Malaria 

Malaria is a life-threatening disease that predominantly strikes sub-Sahara Africa. It is spread through the bite of an infected mosquito. Children under the age of five residing in Africa are affected most by this disease, accounting for 500,000 annual malaria mortalities.

There are four malaria parasites that can cause malaria infection in humans, the most deadly being Plasmodium falciparum. This specific parasite is the deadliest due to its several development life cycle stages with each stage presenting different possible antigens, making it difficult to treat and prevent. It also has a high rate of replication so it takes a short amount of time for infectious particles to build up in the human body. As a result, receiving treatment immediately after infection is crucial for fighting off the disease. Unfortunately, the areas with the highest infection rates do not have easy access to medicine, leading to high mortality rates.

The latest estimate by the World Health Organization (WHO) reported about 207 million cases of malaria in 2012. Though malaria cases predominantly occur in sub-Saharan Africa, 99 countries have ongoing malaria transmission. Early symptoms of malaria include headache, fever, chills, and vomiting. Symptoms usually appear within 10-15 days of receiving the mosquito bite and if left untreated can lead to death.

An estimated 627,000 deaths result from malaria each year, most of which occurred among children residing in Africa. 80% of those deaths occurred in just 14 countries.

There are currently no malaria vaccines to prevent infection and the protective capability of existing treatment and prevention methods are limited. The best treatment presently on the market to treat the malaria strain P. falciparum is artemisinin-based combination therapy (ACT), however, parasite resistance to artemisinins is beginning to emerge and so is resistance to insecticides (prevention method). The only other prevention mechanism in place besides insecticidal nets and sprays is personal protection. As a result, creating an effective malaria vaccine is crucial due to the lack of alternative antimalarial medicines.