A major contributor to this article appears to have a close connection with its subject.(August 2024) |
Company type | Corporation |
---|---|
Industry | Biotechnology |
Founded | 2003 |
Founder | Stephen L. Hoffman |
Headquarters | Rockville, Maryland, United States |
Products | Malaria Vaccines |
Number of employees | 55 |
Website | www.sanaria.com |
Sanaria is a biotechnology company founded to develop whole-parasite vaccines protective against malaria. Sanaria is also developing monoclonal antibodies protective against malaria, vaccines against diarrheal diseases, immunotherapeutics for disease of the liver, and related products for us in malaria research. [1] Sanaria's vaccines are based on the use of the sporozoite (SPZ) stage of the malaria parasite, Plasmodium, as an immunogen, and as a carrier for immunomodulatory molecules.
Sanaria's primary mission is to develop and commercialize whole-parasite PfSPZ vaccines that confer high-level, long-lasting protection against Plasmodium falciparum, the malaria parasite responsible for more than 95% of malaria-associated severe illness and death worldwide and the malaria parasite for which there is the most significant drug resistance. The long term goal is to develop vaccines that prevent all human malaria and use these vaccines to immunize entire populations in geographically defined areas to halt malaria transmission and eliminate malaria. This will be accomplished by first introducing vaccines to prevent malaria in specific populations like pregnant women and children in malaria endemic areas, as well as travelers to malaria endemic areas. [2] [3]
Sanaria moved into its first facility in Rockville, MD in July 2003 supported by a phase I Small Business Innovation Research (SBIR) grant from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) and subsequently by a $4.09M grant from the United States Army Medical Research Acquisition Activity Group to further develop its vaccine. [4] [5] In 2007, Sanaria received a $29.3-million grant from the Bill and Melinda Gates Foundation (BMGF), administered through the PATH Malaria Vaccine Initiative (MVI) which supported the construction of Sanaria's manufacturing facility in Rockville, MD. [6] [7] In 2009, Sanaria received approval from the FDA to test PfSPZ Vaccine in human trials. [6] Sanaria® PfSPZ Vaccine is highly protective against Pf malaria transmitted by controlled human malaria infection (CHMI) and naturally transmitted Pf malaria in Africa for ywo years without intervening booster doses, including during pregnancy. [8] [9] [10] [11] [12] [13] [14] PfSPZ Vaccine received FDA Fast Track Designation in 2016. [15] Sanaria's second generation vaccine, PfSPZ-CVac (CQ) has shown stronger protection against CHMI at a 4-5-fold lower dose. [16] [17] Recently developed Sanaria® PfSPZ-LARC2 Vaccine,is planned to be assessed in clinical trials in late 2024 and 2025 in the US, Germany, and Burkina Faso. [18] It is expected to have the safety profile of PfSPZ Vaccine and as good, if not better, potency/efficacy, as PfSPZ-CVac.
Twenty-two clinical trials of PfSPZ Vaccine(radiation-attenuated SPZ) have been completed or are being conducted in the US, the Netherlands, Germany, Tanzania, Kenya, Mali, Burkina Faso, Gabon, Equatorial Guinea, and Indonesia. Recent results from a study in women of child-bearing potential in Mali [19] [20] showed significant vaccine efficacy (VE) against both malaria infection and clinical malaria over 18 months ranging from 41 to 86% without intervening booster doses. [21] Many of the women participating in the trial became pregnant during follow-up post immunization, and VE during pregnancy against malaria infection was 57% during the two years of follow up. This is the first demonstration of protection against pregnancy malaria by a malaria vaccine. PfSPZ Vaccine is also very safe and well tolerated. In a meta-analysis of safety in 13 randomized, double-blind, placebo-controlled trials, the adverse event profile was no different from that of the normal saline placebo. Based on these results, a new clinical trial will be initiated in 2025 in pregnant Malian women who will be immunized in the second or third trimesters to see if PfSPZ Vaccine is safe during pregnancy and if it will reduce the maternal and fetal morbidity and mortality associated with pregnancy malaria. This study will be conducted by the Malaria Research and Training Center, University of Bamako, and the Laboratory of Malaria Immunology and Vaccinology, NIAID, with Sanaria sponsorship. [22]
Eleven clinical trials of PfSPZ-CVac (chemo-attenuated SPZ) have been conducted in the Netherlands, the US, Germany, Equatorial Guinea, Mali, and Indonesia. In a 2021 article in Nature, two Phase I clinical trials of PfSPZ-CVac were highlighted for efficacy against a malaria parasite, highly variant from the strain in the vaccine, including 100% protection against CHMI at three months after immunization, marking the best protection achieved by a malaria vaccine. [17] [23] [24]
Sanaria is now preparing for first-in-human clinical trials of PfSPZ-LARC2 Vaccine, a genetically attenuated, late-arresting, replication-competent parasite with 2 gene deletions, that should equal or exceed PfSPZ-CVac in potency while having the same safety profile as PfSPZ Vaccine. [25] This new generation parasite is being developed in collaboration with the Seattle Children's Research Institute. [26] It builds on earlier experience with Sanaria’s first genetically altered parasite, Sanaria® PfSPZ-GA1, with a single gene deletion, which was developed in collaboration with the Leiden University Medical Center, and assessed in a clinical trial in the Netherlands. [27] While PfSPZ-GA1 vaccine was safe, it did not offer any advantages over PfSPZ Vaccine (both parasites arrest development early in the liver stages), and is not being pursued further. PfSPZ-LARC2 Vaccine will be assessed in three trials in 2024-25, in Seattle, Washington, in Tübingen, Germany and in Burkina Faso.
Sanaria’s non-attenuated infectious sporozoites, called Sanaria PfSPZ Challenge, is a very important research tool throughout the world. This is the immunogen used in PfSPZ-CVac and can also be used to infect research participants with P. falciparum malaria in order to test the efficacy of vaccines and drugs in a controlled fashion (CHMI), as well as the impact of innate and acquired immunity and genetic background on malaria. The fully infectious sporozoites of PfSPZ Challenge have enabled research teams worldwide to conduct CHMI studies, including in the US, the Netherlands, Germany, United Kingdom, Spain, Tanzania, Kenya, Mali, Gabon, Equatorial Guinea, and the Gambia. [23] [28] [29] In Kenya, 10 PhD students have used data from studies with Sanaria® PfSPZ Challenge to support their PhD thesis work. Sanaria has two variants of PfSPZ Challenge, one from West Africa and one from Brazil, and plans to develop additional variants in the coming years.
Sanaria's research and development is conducted with the collaboration of the International PfSPZ Consortium (I-PfSPZ-C), a group of ~290 investigators and funders from 86 organizations in 28 countries who are dedicated to development of whole PfSPZ malaria vaccines that can be used to prevent malaria in individuals and systematically eliminate malaria from geographically defined areas of the world. [30] [31] The I-PfSPZ-C meets 1-2 times each year to present data, discuss ideas, and map out plans for future studies in an open forum.
In addition to U.S. NIAID, U.S. DoD, and the BMGF, significant funding for development of PfSPZ vaccines has come from the Government of Equatorial Guinea and the corporate social responsibility arms of three U.S. energy companies (Marathon Oil, Noble Energy and AMPCO), Top Institute Pharma (the Netherlands), universities in Nijmegen and Leiden, the Netherlands, the University of Tübingen, the German Centre for Infection Research (DZIF), the Swiss Tropical Public Health Institute and the Swiss Government, and the Tanzanian Commission on Science and Technology. [32] [33] [34] [35] [36]
In 2020, Sanaria Inc. received €12.9M from the European Union Malaria Fund (EUMF) for the development of two malaria vaccines, one malaria prophylactic, and a SARS-CoV-2 vaccine. [37] [38]
Malaria is a mosquito-borne infectious disease that affects vertebrates and Anopheles mosquitoes. Human malaria causes symptoms that typically include fever, fatigue, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. Symptoms usually begin 10 to 15 days after being bitten by an infected Anopheles mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria. The mosquito vector is itself harmed by Plasmodium infections, causing reduced lifespan.
A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.
Plasmodium falciparum is a unicellular protozoan parasite of humans, and the deadliest species of Plasmodium that causes malaria in humans. The parasite is transmitted through the bite of a female Anopheles mosquito and causes the disease's most dangerous form, falciparum malaria. It is responsible for around 50% of all malaria cases. P. falciparum is therefore regarded as the deadliest parasite in humans. It is also associated with the development of blood cancer and is classified as a Group 2A (probable) carcinogen.
A gametocyte is a eukaryotic germ cell that divides by mitosis into other gametocytes or by meiosis into gametids during gametogenesis. Male gametocytes are called spermatocytes, and female gametocytes are called oocytes.
Plasmodium vivax is a protozoal parasite and a human pathogen. This parasite is the most frequent and widely distributed cause of recurring malaria. Although it is less virulent than Plasmodium falciparum, the deadliest of the five human malaria parasites, P. vivax malaria infections can lead to severe disease and death, often due to splenomegaly. P. vivax is carried by the female Anopheles mosquito; the males do not bite.
Plasmodium ovale is a species of parasitic protozoon that causes tertian malaria in humans. It is one of several species of Plasmodium parasites that infect humans, including Plasmodium falciparum and Plasmodium vivax which are responsible for most cases of malaria in the world. P. ovale is rare compared to these two parasites, and substantially less dangerous than P. falciparum.
Plasmodium malariae is a parasitic protozoan that causes malaria in humans. It is one of several species of Plasmodium parasites that infect other organisms as pathogens, also including Plasmodium falciparum and Plasmodium vivax, responsible for most malarial infection. Found worldwide, it causes a so-called "benign malaria", not nearly as dangerous as that produced by P. falciparum or P. vivax. The signs include fevers that recur at approximately three-day intervals – a quartan fever or quartan malaria – longer than the two-day (tertian) intervals of the other malarial parasite.
Merozoitesurface proteins are both integral and peripheral membrane proteins found on the surface of a merozoite, an early life cycle stage of a protozoan. Merozoite surface proteins, or MSPs, are important in understanding malaria, a disease caused by protozoans of the genus Plasmodium. During the asexual blood stage of its life cycle, the malaria parasite enters red blood cells to replicate itself, causing the classic symptoms of malaria. These surface protein complexes are involved in many interactions of the parasite with red blood cells and are therefore an important topic of study for scientists aiming to combat malaria.
Plasmodium knowlesi is a parasite that causes malaria in humans and other primates. It is found throughout Southeast Asia, and is the most common cause of human malaria in Malaysia. Like other Plasmodium species, P. knowlesi has a life cycle that requires infection of both a mosquito and a warm-blooded host. While the natural warm-blooded hosts of P. knowlesi are likely various Old World monkeys, humans can be infected by P. knowlesi if they are fed upon by infected mosquitoes. P. knowlesi is a eukaryote in the phylum Apicomplexa, genus Plasmodium, and subgenus Plasmodium. It is most closely related to the human parasite Plasmodium vivax as well as other Plasmodium species that infect non-human primates.
Malaria prophylaxis is the preventive treatment of malaria. Several malaria vaccines are under development.
Vaccine efficacy or vaccine effectiveness is the percentage reduction of disease cases in a vaccinated group of people compared to an unvaccinated group. For example, a vaccine efficacy or effectiveness of 80% indicates an 80% decrease in the number of disease cases among a group of vaccinated people compared to a group in which nobody was vaccinated. When a study is carried out using the most favorable, ideal or perfectly controlled conditions, such as those in a clinical trial, the term vaccine efficacy is used. On the other hand, when a study is carried out to show how well a vaccine works when they are used in a bigger, typical population under less-than-perfectly controlled conditions, the term vaccine effectiveness is used.
Malaria vaccines are vaccines that prevent malaria, a mosquito-borne infectious disease which affected an estimated 249 million people globally in 85 malaria endemic countries and areas and caused 608,000 deaths in 2022. The first approved vaccine for malaria is RTS,S, known by the brand name Mosquirix. As of April 2023, the vaccine has been given to 1.5 million children living in areas with moderate-to-high malaria transmission. It requires at least three doses in infants by age 2, and a fourth dose extends the protection for another 1–2 years. The vaccine reduces hospital admissions from severe malaria by around 30%.
Pregnancy-associated malaria (PAM) or placental malaria is a presentation of the common illness that is particularly life-threatening to both mother and developing fetus. PAM is caused primarily by infection with Plasmodium falciparum, the most dangerous of the four species of malaria-causing parasites that infect humans. During pregnancy, a woman faces a much higher risk of contracting malaria and of associated complications. Prevention and treatment of malaria are essential components of prenatal care in areas where the parasite is endemic – tropical and subtropical geographic areas. Placental malaria has also been demonstrated to occur in animal models, including in rodent and non-human primate models.
RTS,S/AS01 is a recombinant protein-based malaria vaccine. It is one of two malaria vaccines approved. As of April 2022, the vaccine has been given to 1 million children living in areas with moderate-to-high malaria transmission, with millions more doses to be provided as the vaccine's production expands. 18 million doses have been allocated for 2023-2025. It requires at least three doses in infants by age 2, with a fourth dose extending the protection for another 1–2 years. The vaccine reduces hospital admissions from severe malaria by around 30% and reduces toddler deaths by 15%.
Circumsporozoite protein (CSP) is a secreted protein of the sporozoite stage of the malaria parasite and is the antigenic target of RTS,S and other malaria vaccines. The amino-acid sequence of CSP consists of an immunodominant central repeat region flanked by conserved motifs at the N- and C- termini that are implicated in protein processing as the parasite travels from the mosquito to the mammalian vector. The amino acid sequence of CSP was determined in 1984.
PfSPZ Vaccine is a metabolically active non-replicating whole sporozoite (SPZ) malaria vaccine being developed by Sanaria against Plasmodium falciparum (Pf) malaria. Clinical trials have been safe, extremely well tolerated and highly efficacious. The first generation PfSPZ product is attenuated by gamma irradiation; the second generation vaccines PfSPZ-CVac and PfSPZ LARC2 are, respectively, attenuated chemically and genetically. Multiple studies are ongoing with trials of the PfSPZ vaccines. All three products are produced using the same manufacturing process. These products are stored and distributed below -150 °C using liquid nitrogen (LN2) vapor phase (LNVP) freezers and cryoshippers.
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a family of proteins present on the membrane surface of red blood cells that are infected by the malarial parasite Plasmodium falciparum. PfEMP1 is synthesized during the parasite's blood stage inside the RBC, during which the clinical symptoms of falciparum malaria are manifested. Acting as both an antigen and adhesion protein, it is thought to play a key role in the high level of virulence associated with P. falciparum. It was discovered in 1984 when it was reported that infected RBCs had unusually large-sized cell membrane proteins, and these proteins had antibody-binding (antigenic) properties. An elusive protein, its chemical structure and molecular properties were revealed only after a decade, in 1995. It is now established that there is not one but a large family of PfEMP1 proteins, genetically regulated (encoded) by a group of about 60 genes called var. Each P. falciparum is able to switch on and off specific var genes to produce a functionally different protein, thereby evading the host's immune system. RBCs carrying PfEMP1 on their surface stick to endothelial cells, which facilitates further binding with uninfected RBCs, ultimately helping the parasite to both spread to other RBCs as well as bringing about the fatal symptoms of P. falciparum malaria.
Peter Gottfried Kremsner is a specialist in tropical medicine and Full Professor at the University of Tübingen, Germany. Since 1992 he has been leading the Centre de Recherches Médicales de Lambaréné (CERMEL), Gabon, now as president.
Sanjeev Krishna,, is a British physician and parasitologist whose research focuses on affordable diagnosis and treatment of diseases such as COVID-19, malaria, Ebola, African trypanosomiasis, leishmaniasis, and colorectal cancer. Krishna is Professor of Medicine and Molecular Parasitology at St George's, University of London and St George's Hospital.
Stephen L. Hoffman is an American physician-scientist, tropical medicine specialist and vaccinologist, who is the founder and chief executive and scientific officer of Sanaria Inc., a company dedicated to developing PfSPZ vaccines to prevent malaria.
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