Peter

PETER BEERNINK, PhD
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An Overview

Dr. Beernink’s laboratory is focused on developing improved vaccines for prevention
of disease caused by the bacteria from the genus Neisseria. These microbes colonize mucous membranes, which can lead to invasive infections including sepsis, meningitis, urethritis and other infections. Dr. Beernink’s research includes genetic, biochemical and immunological studies of Neisserial surface antigens, including meningococcal Factor H binding protein (Figure 1). This protein is important for virulence because it recruits complement Factor H to the bacterial surface, which enables the bacteria to evade host immunity.

Figure 1. Structure of Factor H-binding protein (bottom) in a complex with a fragment of human Factor H (top) based on Protein Data Bank entry 2W80 [Schneider et al., 2009. Nature, 458: 890].  The two proteins were separated along the vertical axis to show the respective contact surfaces (color).  The figure was generated with MacPyMol (http://www.pymol.org).

Meningococcal infections are caused by different strains of the bacteria, which are classified into groups based on the sugar coating (“polysaccharide capsule”) that surrounds the bacteria. The polysaccharides from groups A, C, W and/or Y are used in vaccines that are licensed in the U.S. and other countries. These vaccines are highly efficacious against strains from the same groups, however they do not protect against group B strains, which cause a significant burden of disease in the U.S. and Europe, or group X strains, which cause epidemics in sub-Saharan Africa. Recently, two meningococcal vaccines were developed based on protein antigens which are independent of the capsular group; these vaccines are licensed in the U.S., Canada, Australia and/or European Union.

A key antigen in the two protein-based meningococcal vaccines is known as Factor H-binding protein (FHbp). FHbp is a surface antigen that exhibits broad sequence diversity; the three variant groups or two sub-families can be represented in a phylogenic tree (Figure 2). The FHbp ID 1 antigen in one of the licensed vaccines, MenB-4C (Bexsero®, GSK) is divergent from the ID 55 antigen in the same sub-family in the second vaccine MenB-FHbp (Trumenba®, Pfizer). MenB-FHbp also contains an FHbp ID 45 antigen in the other sub-family.

Figure 2

Figure 2. Phylogenic tree depicting 72 of 964 known FHbp amino acid sequence variants using MEGA 7.0 (4). The variants included in the licensed vaccines are labeled in bold and variants expressed by strains that caused recent outbreaks are labeled with smaller numbers. The scale bar indicates five percent sequence divergence.

 

Revised: Wednesday, November 7, 2018 11:06 AM

UCSFBCHO

 


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