Description of Research Expertise

Research Interests
Viral pathogenesis and viral evasion strategies from the host immune response
Recombinant vaccinia viruses as vaccine vectors
Counter-bioterrorism research focusing on smallpox
Monkeypox
Molluscum contagiosum

Key words:
Vaccinia virus, Recombinant vaccines, poxvirus , pathogenesis, smallpox and monkeypox vaccines and therapeutics, molluscum contagiosum

Description of Research
Dr. Isaacs' laboratory focuses on using poxviruses as a model system to study viral proteins that are involved in viral pathogenesis, dissemination, and evasion of the host immune response. Poxviruses, which are used widely as a tool for research and vaccine development, express proteins that inhibit complement activation, bind IL-1, TNF, and interferons, and decrease the host inflammatory response by other mechanisms. Elucidation of these processes could lead to a safer virus vector. Furthermore, the study of these defense molecules encoded by the virus might give insights into the control of inflammation, as well as, the development of new anti-inflammatory drugs. The laboratory has also been pursuing future generation subunit poxvirus vaccines. The lab has been studying protein/adjuvant and mRNA/lipid nanoparticle platforms. Dr. Isaacs was the poxvirus program project leader for the NIH-funded Middle Atlantic Regional Center of Excellence in Biodefense and Emerging Infectious Diseases and was involved in developing a safer smallpox vaccines as well as therapies to treat smallpox and complications from the current smallpox vaccine.

The Isaacs lab is also working with molluscum contagiosum, a poxvirus that causes a very common skin infection, especially in children. This virus has been difficult to study because it cannot be grown in cell culture. The Isaacs lab is pursuing approaches to grow this virus in cell culture systems.

At the VA, Dr, Isaacs is the Local Site investigator for a VA-wide cooperative studies program (CSP) titled "Epidemiology, Immunology, and Clinical Characteristics of COVID-19 (EPIC3) within the Veterans Health Administration."


Lab personnel:
Yuhong Xiao

Past lab personnel:
Asha Abdool
Edward Alexander
Jeanie Chu
Matt Cohen
Brian DeHaven
Xin Fan
Natasha Girgis
Elizabeth Herrara
Heesun Kwak
Shamim Mohammad
Kendra Viner
Jessica Weaver

Selected Publications

Isaacs SN: Asymptomatic Infection? Another Reason to Consider Monkeypox a Disease of Public Health Concern. Ann Intern Med : 2022.

Rao AK, Petersen BW, Whitehill F, Razeq JH, Isaacs SN, Merchlinsky MJ, Campos-Outcalt D, Morgan RL, Damon I, Sánchez PJ, Bell BB: Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022 MMWR Morb Mortal Wkly Rep 71 (22): 734-742,2022.

Xiao, Y., Zeng, Y., Schande, C., Joshi, S.B., Buchman, G.W., Volkin, D.B., Middaugh, C.R., Isaacs, S.N.: Short-term and longer-term protective immune responses generated by subunit vaccination with smallpox A33, B5, L1 or A27 proteins adjuvanted with aluminum hydroxide and CpG in mice challenged with vaccinia virus Vaccine 38 (38): 6007-6018,2020.

Isaacs, S.N.: Monkeypox UpToDate : 2021.

Nuth M, Guan H, Xiao Y, Kulp JL, Parker MH, Strobel ED, Isaacs SN, Scott RW, Reitz AB, Ricciardi RP: Mutation and structure guided discovery of an antiviral small molecule that mimics an essential C-terminal tripeptide of the vaccinia D4 processivity factor Antiviral Research 162 : 178-185,2019.

Guan, H., Nuth, M., Zhukovskaya, N., Saw, Y.L., Bell, E., Isaacs, S.N., Ricciardi, R.P.: A novel target and approach for identifying antivirals against molluscum contagiosum virus Antimicrobial Agents and Chemotherapy 58 (12): 7383-9,2014.

Xiao, Y., Zeng, Y., Alexander, E., Mehta, S., Joshi, S.B., Buchman, G.W., Volkin, D.B., Middaugh, C.R., Isaacs, S.N.: Adsorption of recombinant poxvirus L1-protein to aluminum hydroxide/CpG vaccine adjuvants enhances immune responses and protection of mice from vaccinia virus challenge Vaccine 31 (2): 319-326,2013.

Hudson, P.N., Self, J., Weiss, S., Braden, Z., Xiao, Y., Girgis, N.M., Emerson, G., Hughes, C., Sammons, S.A., Isaacs, S.N., Damon, I.K., Olson, V.A.: Elucidating the role of the complement control protein in monkeypox pathogenicity. PLoS One 7 (4): e35086,2012.

Girgis, N.M., DeHaven, B.C., Xiao, Y., Alexander, E., Viner, K.M., Isaacs, S.N.: The vaccinia virus complement control protein modulates adaptive immune responses during infection. Journal of Virology 85 (6): 2547-56,2011.

Weaver JR, Isaacs SN: Monkeypox virus and insights into its immunomodulatory proteins Immunological Reviews 225 (1): 96-113,2008.

Cohen ME, Xiao Y, Eisenberg RJ, Cohen GH, Isaacs SN: Antibody against Extracellular Vaccinia Virus (EV) Protects Mice through Complement and Fc Receptors PLoS ONE 6 (6): e20597,2011.

Buchman, G.W., Cohen, M.E., Xiao, Y., Richardson-Harman, N., Silvera, P., DeTolla, L.J., Davis, H.J., Eisenberg, R.J., Cohen, G.H., Isaacs, S.N.: A protein-based smallpox vaccine protects non-human primates from a lethal monkeypox virus challenge Vaccine 28 (40): 6627-36,2010.

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Academic Contact Information

Perelman School of Medicine at the University of Pennsylvania
Division of Infectious Diseases
319 Johnson Pavilion
Philadelphia, PA 19104-6073
Phone: 215-573-7515