Stephen L. Hoffman | |
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 Dr. Hoffman in 2024 | |
| Born | Stephen L. Hoffman July 31, 1948 Belmar, New Jersey, U.S. |
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| Scientific career | |
| Fields | Malaria, Vaccinology, Global Health |
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Stephen L. Hoffman (born July 31, 1948) 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.
Hoffman was raised initially in Belmar and subsequently in Ocean Township, Monmouth County, New Jersey. [1] He graduated from Asbury Park High School in 1966, [2] received a BA in political science from the University of Pennsylvania in 1970, an MD from Cornell University Medical College (now Weill Cornell Medicine) in 1975, [3] and a Diploma in Tropical Medicine and Hygiene from the London School of Hygiene and Tropical Medicine in 1978. [4] Additionally in 1978, he completed a residency in Family Medicine at the University of California San Diego. [5] He is board certified in Family Medicine and received a Certificate of Knowledge in Clinical Tropical Medicine and Travelers Health in 1998, and a Doctor of Science (DSc), honoris causa from Monmouth University in 2006. [6] [5]
After completing his residency in 1978, Hoffman was co-founder and director of the Tropical Medicine and Travelers clinic at University Hospital, University of California, San Diego, an adjunct clinical faculty member, and an emergency room physician. [5] In 1980, Hoffman was commissioned as a medical officer in the United States Navy and stationed in Jakarta, Indonesia at the Naval Medical Research Unit Two-Jakarta Detachment where he was the director of the Department of Clinical Investigation and Epidemiology through 1984. His initial focus was on treatment of severe typhoid fever. He proposed and studied the use of high dose dexamethasone in the treatment of severe typhoid fever, which reduced the typhoid fever death rate by more than 80 percent. [7] He also conducted research throughout the Indonesian archipelago on cholera, filariasis, and malaria. [5] [3] In 1987, Hoffman returned to Bethesda, MD, and served as the director of the Malaria Program at the Naval Medical Research Institute (later Naval Medical Research Center) until 2001. Hoffman and his team worked on identifying the targets and mechanisms of protective immunity against malaria and malaria vaccine development. They were the first in the world to test a DNA vaccine in normal humans and demonstrate that DNA vaccines elicited killer T cell responses. [8] Hoffman also led the team that sequenced the Plasmodium falciparum genome. [9]
After retiring from the Navy, Hoffman spent two years as senior vice president of biologics at Celera Genomics, the company that sequenced the human genome. Hoffman worked with utilizing human genomics and proteomics to develop immunotherapies and vaccines against cancer and to establish the potential for the field of personalized medicine. He also organized the sequencing of the genome of Anopheles gambiae . [10]
In 2003 Hoffman founded Sanaria Inc. to develop whole sporozoite malaria vaccines and has since been the chief executive and scientific officer of Sanaria Inc. [11]
Hoffman has over 500 scientific publications. He has made major contributions in the following areas.
Hoffman is married to B. Kim Lee Sim, PhD, a molecular biologist, who is the founder and president of Protein Potential LLC and executive vice president of Sanaria Inc. [45] They have three children (Alexander [JD], [46] Seth [MD], [47] and Benjamin [MD, PhD] [48] ).
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.
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. 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 trophozoite is the activated, feeding stage in the life cycle of certain protozoa such as malaria-causing Plasmodium falciparum and those of the Giardia group. The complementary form of the trophozoite state is the thick-walled cyst form. They are often different from the cyst stage, which is a protective, dormant form of the protozoa. Trophozoites are often found in the host's body fluids and tissues and in many cases, they are the form of the protozoan that causes disease in the host. In the protozoan, Entamoeba histolytica it invades the intestinal mucosa of its host, causing dysentery, which aid in the trophozoites traveling to the liver and leading to the production of hepatic abscesses.
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 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 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 malaria in pregnancy which is life-threatening to both pregnant women and unborn fetuses. PAM occurs when a pregnant woman contracts malaria, generally as a result of Plasmodium falciparum infection, and because she is pregnant, is at greater risk of associated complications such as placental malaria. Placental malaria interferes with the transmission of vital substances through the fetal placenta, which can result in stillbirths, miscarriages, and dangerously low birth weights.
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%.
Russell J. Howard is an Australian-born executive, entrepreneur and scientist. He was a pioneer in the fields of molecular parasitology, especially malaria, and in leading the commercialisation of one of the most important methods used widely today in molecular biology today called “DNA shuffling" or "Molecular breeding", a form of "Directed evolution".
Jonathan James Juliano is an American physician/scientist. He currently works at UNC School of Medicine.
Plasmodium coatneyi is a parasitic species that is an agent of malaria in nonhuman primates. P. coatneyi occurs in Southeast Asia. The natural host of this species is the rhesus macaque and crab-eating macaque, but there has been no evidence that zoonosis of P. coatneyi can occur through its vector, the female Anopheles mosquito.
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.
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. 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.
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.
Elizabeth Ann Winzeler is an American microbiologist and geneticist. She is a professor in the Division of Host-Microbe Systems and Therapeutics of the School of Medicine at the University of California at San Diego. Although she works in a variety of different disease areas, most research focuses on developing better medicines for the treatment and eradication of malaria.
Joseph Michael Vinetz is a Professor of Medicine and Anthropology at Yale University, Research Professor at the Universidad Peruana Cayetano Heredia and Associate Investigator of the Alexander von Humboldt Institute of Tropical Medicine at the Universidad Peruana Cayetano Heredia.
David A. Fidock, is the CS Hamish Young Professor of Microbiology and Immunology and Professor of Medical Sciences at Columbia University Irving Medical Center in Manhattan.
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