Principal Investigator: Willie F. Vann, PhD
Office / Division / Lab: OVRR / DBPAP / LBP

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General Overview

Disease-causing bacteria coat themselves with a variety of complex chains of sugar molecules called polysaccharides. These polysaccharide coats are essential for the survival of these bacteria in the human blood stream. Since these structures are important for survival of bacteria in the blood stream they are perfect targets the body's defense mechanisms. Scientists have learned that these polysaccharide chains can be made into effective vaccines against disease causing microorganisms.

Our laboratory is studying how bacteria make these polysaccharide coats so we can develop new techniques to make vaccines against bacteria coated with these polysaccharides. Specifically, we are investigating new ways to prepare and analyze vaccines prepared from bacterial polysaccharide coats using molecular biology and biochemical techniques. What we learn from this work will be of great help to us in understanding and evaluating current and future techniques for manufacturing carbohydrate vaccines.

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Scientific Overview

Bacterial pathogens are often coated with polysaccharide virulence factors and some pathogens produce toxins that bind to host oligosaccharides using those host molecules as receptors for entry into the cell. These polysaccharides and toxins are excellent targets for preventing and controlling disease. Indeed, both polysaccharides and polysaccharides conjugated to inactivated toxins are the key components of vaccines that are very effective in preventing disease caused by Haemophilus influenzae, Streptococcus pneumonia, and several serogroups (i.e., "variations of") of Neisseria meningitidis.

The goals of this research project are 1) to determine the metabolic pathway for the synthesis of polysaccharides in gram negative pathogens and use this knowledge to develop methods for preparing glycoconjugate vaccines using metabolic engineering; and 2) to improve the manufacture of current conjugate vaccines through the investigation of conjugation chemistry.

While the currently licensed polysaccharide vaccines have been successful, manufacture and control of quality and efficacy of these products present regulatory challenges due to lack of a detailed definition of the immunogens. The novel technology developed and knowledge gained by this work will help to us to better characterize vaccines and predict if alternative vaccines will be effective.

In recent years workers and manufacturers in the vaccine field have begun to employ metabolic engineering technologies to develop vaccines against the carbohydrate structures on pathogens for which no current vaccine exist. Our work in the research program described here will provide us with the necessary expertise to evaluate these new vaccines.

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Publications

Sci Rep 2020 Feb 20;10(1):3032
Preclinical development of a fusion peptide conjugate as an HIV vaccine immunogen.
Ou L, Kong WP, Chuang GY, Ghosh M, Gulla K, O'Dell S, Varriale J, Barefoot N, Changela A, Chao CW, Cheng C, Druz A, Kong R, McKee K, Rawi R, Sarfo EK, Schon A, Shaddeau A, Tsybovsky Y, Verardi R, Wang S, Wanninger TG, Xu K, Yang GJ, Zhang B, Zhang Y, Zhou T, The VRC Production Program, Arnold FJ, Doria-Rose NA, Lei QP, Ryan ET, Vann WF, Mascola JR, Kwong PD

mSphere 2019 Sep 25;4(5):e00520-19
Glycoconjugates: what it would take to master these well-known yet little-understood immunogens for vaccine development.
Avci F, Berti F, Dull P, Hennessey J, Pavliak V, Prasad AK, Vann W, Wacker M, Marcq O

Glycobiology 2018 Feb 1;28(2):100-7
Interaction of Neisseria meningitidis Group X N-acetylglucosamine-1-phosphotransferase with its donor substrate.
Ming SA, Cottman-Thomas E, Black NC, Chen Y, Veeramachineni V, Peterson DC, Chen X, Tedaldi LM, Wagner GK, Cai C, Linhardt RJ, Vann WF

FEBS J 2017 Jun;284(11):1688-99
In vitro generation of polysialylated cervical mucins by bacterial polysialyltransferases to counteract cytotoxicity of extracellular histones.
Galuska SP, Galuska CE, Tharmalingam T, Zlatina K, Prem G, Husejnov FC, Rudd PM, Vann WF, Reid C, Vionnet J, Gallagher ME, Carrington FA, Hassett SL, Carrington SD

Chembiochem 2017 Apr 18;18(8):799-815
Conjugate vaccines from bacterial antigens by squaric acid chemistry: a closer look.
Xu P, Kelly M, Vann WF, Qadri F, Ryan ET, Kovac P

PLoS Negl Trop Dis 2015 Jul 8;9(7):e0003881
A cholera conjugate vaccine containing O-specific polysaccharide (OSP) of V. cholerae O1 inaba and recombinant fragment of tetanus toxin heavy chain (OSP:rTTHc) induces serum, memory and lamina proprial responses against OSP and is protective in mice.
Sayeed MA, Bufano MK, Xu P, Eckhoff G, Charles RC, Alam MM, Sultana T, Rashu MR, Berger A, Gonzalez-Escobedo G, Mandlik A, Bhuiyan TR, Leung DT, LaRocque RC, Harris JB, Calderwood SB, Qadri F, Vann WF, Kovac P, Ryan ET