Jeffrey J. Adamovicz
Director, Laboratory of Infectious Disease Research, Associate Professor Veterinary Pathobiology
Building Address: University of Missouri, College of Veterinary Medicine, Department of Veterinary Pathobiology, 209D Connaway Hall, Columbia, MO 65211-5130
Phone Number: 573 882-3261
Lab Website: http://rbl.missouri.edu/
Research Emphasis: I have broad interests in infectious disease and microbiology. I continue to be fascinated and drawn to both newly emerging diseases such as Zika virus and canine dysautonomia as well as better understood pathogens such as the causative agents of plague, anthrax and tularemia. My current research interests are in the development of vaccines for zoonotic diseases and the pathogenesis of facultative intracellular bacteria. Recently I have been interested in a new brucellosis vaccine for cattle and to develop a better understanding of the bovine immune response to brucellosis and other facultative intracellular bacteria. To that end and by extension my laboratory research program has worked on developing new methods and evaluating novel data over the past three years. These research goals are important as there is a paucity of published information on the immune systems of the host animal species for brucellosis and a clear need for a better brucella vaccine. The nature of this work is long-term and heavily regulated resulting in long lead times between initiation, completion and publication of results.
We have embarked on both bovine vaccine studies with the current brucellosis vaccine (RB51) and the development of a small animal model chimera which we hope to engraft the bovine/elk immune system. This will allow us to study the host immune response to brucellosis in a small animal model platform.
I also have continuing interest in immunity to Y. pestis and other facultative intracellular bacteriaparticularly the role of DCs as vaccine targets or as targets to alter the pathogenesis of disease. There is a paucity of data on how bacteria interact with dendritic cells and thwart both innate and adaptive immune functions. We are interested in defining methodologies to select and test important T cell epitopes which will induce more effective T cell responses to facultative intracellular bacteria.
The development of a brucellosis vaccine for cattle is a strategic goal of the USDA and CABs. Towards this end we first choose to test the current vaccine RB51 in multiple doses. RB51 vaccination is currently a single dose calf-hood vaccine. This effort began in 2012 in and continues. Our initial studies were to evaluate of the role of CMI in efficacy of Experimental Alternate Schedule of Live Attenuated RB51 Vaccine against Brucellosis in Cattle. We have completed this project recently and our data show that multi-dose RB51 vaccination prevents vertical transmission and significantly lowers bacterial burden in the multi-dose treated cows. In particular our data show that vaccine boosting during pregnancy does not induce abortion as was previously thought. We seek to extend these studies to better define the bovine immune response to RB51 and or develop more defined sub-unit vaccines for brucellosis.
Xenograft Mouse Model
This research project’s goals were to perform pilot studies for the xenografting of bovine or cervid hematopoietic stem cells into severely immune-compromised NOG mice. We hope to develop these mice as surrogates for their respective host species to use to test new brucellosis vaccine candidates. Thus this project supports our overall emphasis on brucellosis vaccine development. To date we have been able to graft one set of mice with human stem cells as a proof of principal and were able to detect peripheral T cells. We have conducted two experiments with bovine derived stem cells but were not able to detect cells as a result of mouse deaths in one trial and poor recovery of stem cells in the other. More recently we have been able to engraft bovine and elk stem cells in separate experiments. These experiments will continue, with a focus on characterization of the engrafted cell types. The development of new animal models is an unmet need in brucellosis research.
Dendritic Cell (DC) Biology and Immunity to B. abortus.
Understanding the role of DCs in infection and in particular infection with B. abortus is an understudied area but critical to develop an understanding of immunity to this facultative intracellular pathogen. Our efforts this year were focused on in vitro studies of monocyte derived or stem cell derived DC precursors.
Our hypothesis is that RB51 infected DCs can stimulate cognate T cells and improve CMI. This stimulation may be enhanced with TLR agonists. This past year we have worked to develop immortalized DC subsets, established an MOI value for monocyte derived DCs exposed to RB51 vaccine strain, established an improved bovine DC yield from bovine stem cells and demonstrated activation of T cells derived from RB51 vaccinated cattle by bovine derived DCs.
MPT faculty member
CMP faculty member
Selected Publications: Use links to citations (i.e., abstracts) in PubMed, if you wish to science have focused on the development of vaccines for zoonotic bacterial diseases. Most important in the development and testing of next generation vaccines for plague and anthrax. I had begun this work in the 1995, at this time there were no effective vaccines available against inhalation plague and not much was understood about immune mechanisms of protection. An effective vaccine against inhalation anthrax was available but was criticized for it’s reactegenicity and extensive and lengthy dose regimen. We undertook basic and applied research to develop a de novo vaccine for plague and an improved vaccine for anthrax. The focus on both vaccines was preliminary efficacy data followed by robust product development studies to create IND products and then to assist advanced development of these medical products through full FDA licensure. Both vaccine candidates were submitted as investigational new drugs and have completed phase three clinical trials.
Earliest publications were on development and testing of novel recombinant plague vaccine:
Heath, D.G., G.W. Anderson, Jr., J.M. Mauro, S.L. Welkos, G.P. Andrews, J. Adamovicz, A.M. Friedlander. (1998). Protection against experimental bubonic and pneumonic plague by a recombinant capsular F1-V antigen fusion protein vaccine. Vaccine 16:1131-1137.
Andrews, G.P., S. Strachan, G.E. Benner, A.K. Sample, G.W. Anderson Jr., J.J. Adamovicz, S.L. Welkos, J.K. Pullen, A.M. Friedlander. (1999). Protective efficacy of recombinant Yersinia outer proteins against bubonic plague caused by encapsulated and non-encapsulated Yersinia pestis. Infect Imm 67:1533-1537.
Jarrett, C.O., F. Sebbane, J.J. Adamovicz, G.P. Andrews, B.J. Hinnebusch. (2004). A flea-borne transmission model to evaluate vaccine efficacy against naturally acquired bubonic plague. Infect Imm 72:2052-2056.
Publications on scalable improvements for manufacture of plague vaccine and vaccine regimen:
Powell, B.S., G.P. Andrews, J.T. Enama, S. Jendrek, C. Bolt, P. Worsham, J.K. Pullen, W. Ribot, H. Hines, L. Smith, D.G. Heath, J.J. Adamovicz. (2005). Design and testing for a non-tagged F1-V fusion protein as vaccine antigen against bubonic and pneumonic plague. Biotech Prog 21:1490-1510.
A. Glynn, C.J. Roy, B.S. Powell, J.J. Adamovicz, L.C. Freytag, J.D. Clements. (2005). Protection against aerosolized Yersinia pestis challenge following homologous and heterologous prime-boost with plague antigens. Infect Imm73:5256-5261.
J.L. Goodin, D.F. Nellis, B.S. Powell, V.V. Vyas, J.T. Enama, L.C. Wang, P.K. Clark, S.L. Giardina, J.J. Adamovicz, D.F. Michiel. (2007). Purification and protective efficacy of monomeric and modified Yersinia pestis Capsular F1-V Fusion Proteins for Vaccination against Plague. Protein Expression and Purification 53:63-79.
P.A. Arlen, M. Singleton, J.J. Adamovicz, Y. Ding, A. Davoodi-Semiromi, H. Daniell. (2008). Effective plague vaccination via oral delivery of plant cells expressing F1-V antigens in chloroplasts. Infect Immun. 76:3640-50.
Publications on mechanisms of protective immunity and immune correlates development:
Parent, M.A., K.N. Berggren, I.K. Mullarky, F.M. Szaba, L.W. Kummer, J.J. Adamovicz, S.T. Smiley. (2005). Yersinia pestis V protein epitopes recognized by CD4 T cells. Infect Imm 73:2197-2204.
T. Jones, J.J. Adamovicz, S.L. Cyr, C.R. Bolt, N. Bellerose, L.M. Pitt, G.H. Lowell, D.S. Burt (2006). Intranasal proteosomeTM-based F1-V vaccine elicits respiratory and serum antibody responses and protects mice against lethal aerosolized plague infection. Vaccine 24:1625-1632.
J. Bashaw, S. Norris, S. Weeks, S. Trevino, J.J. Adamovicz, S. Welkos. (2007). Development of in vitro correlate assays of immunity to infection with Yersinia pestis. Clin. Vaccine Immunol. 14:605-16.
S. Welkos, S. Norris, J. Adamovicz. (2008). A modified caspase-3 assay correlates with immunity of nonhuman primates to infection by Yersinia pestis. Clin Vaccine Immunol. 15:1134-37.
S.F. Little, W.M. Webster, H. Wilhelm, B. Powell, J. Enama, J.J. Adamovicz. (2008). Evaluation of quantitative anti-F1 IgG and anti-V IgG ELISAs for use as an in-vitro based potency assay of plague vaccine in mice. Biologicals. 36:287-95.
P. Fellows, J. Adamovicz, J. Hartings, R. Sherwood, W. Mega, T. Brasel, E. Barr, L. Holland, W. Lin, A. Rom, W. Blackwelder, J. Price, S. Morris, D. Snow, M.K. Hart (2010). Protection in mice passively immunized with serum from cynomolgus macaques and humans vaccinated with recombinant plague vaccine (rF1V). Vaccine. Nov16;28(49):7748-56
S. Lin, S. Park, J.J. Adamovicz, J. Hill, J.B. Bliska, C.K. Cote, D.S. Perlin, K. Amemiya, S.T. Smiley. (2010). TNF- and IFN- contribute to F1/LcrV-targeted immune defense in mouse models of fully virulent pneumonic plague. Vaccine. Dec16;29(2):357-62
C.Y. Lindsey, S.F. Little, S. Norris, B. Powell, J.J. Adamovicz*. (2012). Validation of quantititative ELISA for the measurement of anti-Yersinia pestis F1 and V antibody concentration in non-human primate sera. J. Immuno Assays & Immunochem. Jan;33(1):91-113
Anthrax publications on characterization of recombinant protective antigen:
B. Powell, W. Ribot, J. Adamovicz, G. Andrews. (2004). Structural Characterizations of Protein Antigens for the Next Generation Vaccines against Anthrax and Plague. U.S. Government Technical Report
W. J. Ribot, B. S. Powell, B. E. Ivins, , S. Little, W. M. Johnson, T. A. Hoover, S.L. Norris, J. Adamovicz, A.M. Friedlander, and G. P. Andrews. (2006). Comparative efficacy of protective antigen isoform vaccines against Bacillus anthracis spore challenge in rabbits. Vaccine 24:3469-3476.
B.S. Powell, J. T. Enama, W.J. Ribot, W.M. Webster, S. Little, T. Hoover, J.J. Adamovicz, G.P. Andrews. (2007). Multiple Asparagine Deamidation of Bacillus anthracis Protective Antigen Causes Charge Isoforms whose Complexity Correlates with Reduced Biological Activity. Proteins: Structure, Function and Bioinformatics. 68:458-79.
U.S. 10/987,533 and PCT/US2004/38480 filed 11/12/2004. Awarded 18 May 2010 #7,718,779; Prophylactic, and therapeutic monoclonal antibodies (specific for the virulence (V) antigen of Yersinia pestis). Tran C. Chanh, Gerald P. Andrews, Jeffrey J. Adamovicz and Bradford S. Powell.
Full list of publications is available at Research Gate: