Antigenic Variation in Microbial Evasion of Immune Responses

Abstract

Antigenic variation is the means by which a number of highly pathogenic microorganisms, ranging from the electronmicroscopic human viruses to bacteria to fungi and unicellular protozoan parasites, passively evade immune surveillance. Through the understanding of the growing variety of mechanisms of the antigenic variation of surface proteins, it has become possible for us to determine what is preventing the host organism from mounting an effective immune response. Antigenic variation has serious public health consequences, for example, the current human immunodeficiency virus pandemic and the looming influenza pandemic, as well as a significant challenge to developing vaccines capable of eliciting long‐lasting or life‐long protective immunity against several pathogens.

Key Concepts:

  • Antigenic variation is a major mechanism of passively evading the host immune surveillance.

  • Antigenic variation is exhibited by a number of highly pathogenic microorganisms including human viruses, bacteria, fungi and unicellular protozoans.

  • Antigenic variation poses challenges to vaccine development against microorganisms causing major public health problems globally.

  • HIV‐1 surface glycoproteins display antigenic variation due to a high mutation rate during replication and significant tolerance of the variation.

  • Heterochromatin in the chromososome ends (telomers) in the malarial parasites mediate epigenetic regulation in the malaria parasite Plasmodium falciparum.

  • African trypanosomes control antigenic variation by periodically switching its variant surface glycoprotein involving transposition followed by recombination occurring at the telomeric expression site.

  • Targeting conserved regions of surface glycoproteins by using broadly neutralising antibodies against highly conserved exposed sites in surface proteins.

  • Targeting the oligosaccharides on surface glycoproteins, such as by the use of enveloped virus neutralising compounds (EVNCs).

Keywords: mutation; antigenic drift and shift; pandemic; gene switching; gene duplication; challenges to vaccine design

Figure 1.

Surface variation in trypanosomes. (a) Mechanism of transposition of trypanosomes in developing a large repertoire of VSGs. (b) Levels of antibody response following trypanosome infection. The level of antibody peaks after surface expression of the corresponding VSG has ceased.

Figure 2.

Proposed model for the broad‐spectrum neutralising, prophylactic and preventive oral vaccine against retroviruses (HIV and influenza). HIV and influenza (and their subtypes) surface glycoproteins play an important role in the pathogenesis mediated by these viruses. Owing to constant mutations in the cell surface glycoproteins, neutralising antibodies targeting one glycoprotein may not necessarily work against other isolates of the virus. Both pomegranate juice and fulvic acid contain acidic compounds. These compounds may bind to the lipid or the sugar chains on glycoproteins, and thereby neutralise the surface of the viruses and their isolates making them avirulant. These less virulant viruses may serve as antigens for the candidate vaccines. Unlike, neutralising antibodies, which target only one glycoprotein, the compounds may bind to most of the glycoproteins, an action, which makes them broad‐spectrum inhibitors of HIV, influenza and their subtypes.

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Kotwal, Girish J, and Kulkarni, Amod P(May 2013) Antigenic Variation in Microbial Evasion of Immune Responses. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001207.pub3]