Primary Appointment:
 Department of Medicine

GEBS Cluster Affiliations:
 Immunology, Microbiology, and Virology - IMV

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 689
Rochester, New York 14642

Phone: (585) 275-5871
E-Mail: john_treanor@urmc.rochester.edu

Novel Viral Vaccines and Antivirals

Clinical studies on a novel inhibitor of influenza virus (GG167): GG 167 is an inhibitor of the influenza virus neuraminidase, which binds to the active site of the enzyme with high affinity. GG167 was designed partly based on the crystal structure of the influenza virus neuraminidase and is therefore often cited as an example of "rational" drug design. Because the drug is designed to interact with a highly conserved region of the neuraminidase, it has been theorized that drug resistant mutants would be isolated infrequently. So far, this seems to be true. Viruses which are resistant to the inhibitory effects of GG167 can be isolated relatively easily in cell culture. However, GG167 remains active in animals infected with these "resistant" mutants. This is because the mechanism of in vitro drug resistance appears to involve second site mutations in the hemagglutinin gene which allow the virus to utilize a method of egress from the cell that is not available in vivo. Truly resistant viruses have not been seen in clinical studies so far. To date, we have done three studies of GG167 in humans. These have included human challenge studies with infectious influenza A virus; our studies remain ongoing.

Other Studies: Other studies are centered on clinical studies to evaluate experimental measures to control viral diseases, particularly influenza. The laboratory component of this is applied laboratory studies to support the clinical vaccine and drug trials.

Miller GE, Cohen S, Pressman S, Barkin A, Rabin BS, Treanor JJ. Psychological stress and antibody response to influenza vaccination: when is the critical period for stress, and how does it get inside the body? Psychosom Med. 66:215-23, 2004.

Belshe RB, Newman FK, Frey SE, Couch RB, Treanor JJ, Tacket CO, Yan L. Dose-dependent neutralizing-antibody responses to vaccinia. J Infect Dis. 189:493-7, 2004.

Anderson P, Treanor J, Porcelli S, Pichichero M. Non-interference between two protein carriers when used with the same polysaccharide for pneumococcal conjugate vaccines in 2-year-old children. Vaccine 21:1554-9, 2003.

Bernstein DI, Yan L, Treanor J, Mendelman PM, Belshe R. Effect of yearly vaccinations with live, attenuated, cold-adapted, trivalent, intranasal influenza vaccines on antibody responses in children. Pediatr Infect Dis J. 22:28-34, 2003.

Pichichero ME, Cernichiari E, Lopreiato J, Treanor J. Mercury concentrations and metabolism in infants receiving vaccines containing thiomersal: a descriptive study. Lancet. 360:1737-41, 2002.

Frey SE, Couch RB, Tacket CO, Treanor JJ, Wolff M, Newman FK, Atmar RL, Edelman R, Nolan CM, Belshe RB. Clinical responses to undiluted and diluted smallpox vaccine. N Engl J Med. 346:1265-74, 2002.

Shelly MA, Pichichero ME, Treanor JJ. Low baseline antibody level to diphtheria is associated with poor response to conjugated pneumococcal vaccine in adults. Scand J Infect Dis. 33:542-4, 2001.

Treanor JJ, Wilkinson BE, Masseoud F, Hu-Primmer J, Battaglia R, O'Brien D, Wolff M, Rabinovich G, Blackwelder W, Katz JM. Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans. Vaccine 19:1732-7, 2001.

Treanor JJ, Hayden FG, Vrooman PS, Barbarash R, Bettis R, Riff D, Singh S, Kinnersley N, Ward P, Mills RG. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA. 283:1016-24, 2000.

Betts RF, Treanor JJ. Approaches to improved influenza vaccination. Vaccine. 18:1690-5, 2000.

Treanor JJ, Kotloff K, Betts RF, Belshe R, Newman F, Iacuzio D, Wittes J, Bryant M. Evaluation of trivalent, live, cold-adapted (CAIV-T) and inactivated (TIV) influenza vaccines in prevention of virus infection and illness following challenge of adults with wild-type influenza A (H1N1), A (H3N2), and B viruses. Vaccine 18:899-906, 1999.

Hayden FG, Treanor JJ, Fritz RS, Lobo M, Betts RF, Miller M, Kinnersley N, Mills RG, Ward P, Straus SE. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA 282:1240-6, 1999.

Tasker SA, Treanor JJ, Paxton WB, Wallace MR. Efficacy of influenza vaccination in HIV-infected persons. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 131:430-3, 1999.