Stephen L. Hoffman


Stephen L. Hoffman MD, DTMH, CAPT, MC, USN is the founder and CEO of Sanaria, Inc.

Early life and education

Hoffman was raised initially in Belmar and subsequently in Ocean Township, Monmouth County, New Jersey. He graduated from Asbury Park High School in 1966, received a BA in political science from the University of Pennsylvania in 1970, an MD from Cornell University Medical College in 1975, and a Diploma in Tropical Medicine and Hygiene from the London School of Hygiene and Tropical Medicine in 1978. Additionally in 1978, he completed a residency in Family Medicine at the University of California San Diego. 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, honoris causa from Monmouth University in 2006.

Professional career

Work experience

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. 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. He also conducted research throughout the Indonesian archipelago on cholera, filariasis, and malaria. In 1987, Hoffman returned to Bethesda, MD, and served as the director of the Malaria Program at the Naval Medical Research Institute 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. Hoffman also led the team that sequenced the Plasmodium falciparum genome.
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.
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.

Contributions to science and technology

Hoffman has over 500 scientific publications. He has made major contributions in the following areas.
  • Treatment of severe typhoid fever. He established that high dose dexamethasone treatment reduced mortality of severe typhoid fever by more than 80%.
  • Understanding of pre-erythrocytic stage protective immunity against malaria. He reported the first demonstration of killing of infected hepatocytes by malaria sporozoite specific T cells, the first demonstration of human cytotoxic T lymphocytes against any parasite, and the complexity of protective immunity at this stage of the parasite life cycle.
  • Development of DNA vaccines and prime boost approaches. He conducted the first trial of a DNA or any other nucleotide vaccine in a normal human and made the first demonstration that a DNA vaccine induced CD8+ cytotoxic T cells in humans.
  • Sequencing of the genomes of Plasmodium falciparum, the parasite that causes more than 98% of deaths from malaria and Anopheles gambiae, the major malaria transmitting mosquito in Africa. He was the senior author on the papers reporting the sequences of the first Plasmodium falciparum chromosome and of Anopheles gambiae, the major mosquito vector of malaria in Africa.
  • Development of whole sporozoite malaria vaccines. It has been known since the 1970s that immunization of humans by bite of mosquitoes infected with radiation attenuated P. falciparum sporozoites protects these individuals. Malaria vaccine development always relied on creating subunit vaccines to try to duplicate this immunity, because it was thought to be impossible to produce a whole sporozoite vaccine that met regulatory and cost of goods standards. Hoffman conceived of the idea of developing an injectable sporozoite vaccine, and he and his team developed all the technology to manufacture whole sporozoite vaccines. Immunization with the radiation-attenuated PfSPZ Vaccine and the chemo-attenuated PfSPZ- CVac, have both been shown to induce 100% protective immunity in humans, protection that has now been shown to be durable for at least 18 months, and effective against the heterogeneous P. falciparum parasites found in high transmission areas of Mali and Burkina Faso. An international consortium has been established that has and will continue to run clinical trials at 5 sites in the U.S., Germany, 5 countries in Europe, 7 countries in Africa, and Indonesia, and is planning to submit a PfSPZ vaccine for licensure in 2028.

Awards and distinctions

Awards

Memberships

Personal life

Hoffman is married to B. Kim Lee Sim, PhD, a molecular biologist, who was the founder and president of Protein Potential LLC and is current executive vice president of Sanaria Inc. They have three children.

Selected publications

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  • Epstein JE, Tewari K, Lyke KE, Sim BK, Billingsley PF, Laurens MB, Gunasekera A, Chakravarty S, James ER, Sedegah M, Richman A, Velmurugan S, Reyes S, Li M, Tucker K, Ahumada A, Ruben AJ, Li T, Stafford R, Eappen AG, Tamminga C, Bennett JW, Ockenhouse CF, Murphy JR, Komisar J, Thomas N, Loyevsky M, Birkett A, Plowe CV, Loucq C, Edelman R, Richie TL, Seder RA, and Hoffman SL. Live attenuated malaria vaccine designed to protect through hepatic CD8 T cell immunity. Science 334: 475–480, 2011.
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  • Mordmuller B, Surat G, Lagler H, Chakravarty S, Ishizuka AS, Lalremruata A, Gmeiner M, Campo JJ, Esen M, Ruben AJ, Held J, Calle CL, Mengue JB, Gebru T, Ibanez J, Sulyok M, James ER, Billingsley PF, Natasha KC, Manoj A, Murshedkar T, Gunasekera A, Eappen AG, Li T, Stafford RE, Li M, Felgner PL, Seder RA, Richie TL, Sim BK, Hoffman SL, and Kremsner PG. Sterile protection against human malaria by chemoattenuated PfSPZ vaccine. Nature 542: 445–449, 2017.
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