Abstract
Vaccinia Virus (VACV) is an enveloped double stranded DNA virus and the active ingredient of the smallpox vaccine. The systematic administration of this vaccine led to the eradication of circulating smallpox (variola virus, VARV) from the human population. As a tribute to its success, global immunization was ended in the late 1970s. The efficacy of the vaccine is attributed to a robust production of protective antibodies against several envelope proteins of VACV, which cross-protect against infection with pathogenic VARV. Since global vaccination was ended, most children and young adults do not possess immunity against smallpox. This is a concern, since smallpox is considered a potential bioweapon. Although the smallpox vaccine is considered the gold standard of all vaccines and the targeted antigens have been widely studied, the epitopes that are targeted by the protective antibodies and their mechanism of binding had been, until recently, poorly characterized. Understanding the precise interaction between the antibodies and their epitopes will be helpful in the design of better vaccines against other diseases. In this review we will discuss the structural basis of recognition of the immunodominant VACV antigens A27, A33, D8, and L1 by protective antibodies and discuss potential implications regarding their protective capacity.
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Abbreviations
- VACV:
-
Vaccinia virus
- VARV:
-
variola virus
- MPXV:
-
monkeypox virus
- ECTV:
-
ectromelia virus
- MAb:
-
monoclonal antibody
- IMV:
-
intracellular mature virus
- EEV:
-
extracellular enveloped virus
- GAG:
-
glycosaminoglycan
- HS:
-
heparan sulfate
- CS:
-
chondroitin sulfate
- GlcA:
-
glucuronic acid
- GalNAc:
-
N-acetyl galactosamine
- HC:
-
heavy chain
- LC:
-
light chain
- CDR:
-
complementarity determining region
- H:
-
hydrogen (bond)
- vdW:
-
van der Waals
- BSA:
-
buried surface area
- sc:
-
shape correlation
- Fab:
-
fragment of antigen binding
- KD :
-
equilibrium binding constant
- EFC:
-
entry fusion complex
- SAM:
-
single alanine scanning mutagenesis
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Acknowledgements
I would like to thank Bjoern Peters, Yan Xiang, Shane Crotty and Mark Buller for a terrific collaboration and all lab members, especially Michael H. Matho, Tom Kaever, Xiangzhi Meng and Andrew Schlossman without whom the studies would have been nearly impossible. Many thanks also to Yan Xiang for critically reading the manuscript. This project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract no. HHSN272200900048C
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Zajonc, D.M. (2017). Antibody Recognition of Immunodominant Vaccinia Virus Envelope Proteins. In: Harris, J., Marles-Wright, J. (eds) Macromolecular Protein Complexes. Subcellular Biochemistry, vol 83. Springer, Cham. https://doi.org/10.1007/978-3-319-46503-6_4
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