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Antigenic breadth: a missing ingredient in HSV-2 subunit vaccines?

William P Halford1

  • 1Department of Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA.

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PubMed
Summary

Live herpes simplex virus 2 (HSV-2) vaccines, expressing 99% of viral antigens, may be more effective than subunit vaccines. Review suggests these live vaccines could combat genital herpes, despite past safety concerns hindering trials.

Keywords:
alum + monophosphoryl lipid A adjuvantantigenic breadthdeletion of ICP0’s nuclear localization signalglycoprotein Dherpes simplex virus 2infected cell protein 0live HSV-2 vaccineplaque-forming unitsevere-combined immunodeficiency

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Area of Science:

  • Virology
  • Vaccinology
  • Immunology

Background:

  • Subunit vaccines for human papillomavirus and hepatitis B virus utilize single viral proteins.
  • Herpes simplex virus 2 (HSV-2) has a significantly larger genome, meaning single-protein vaccines cover only a small antigenic fraction.
  • Previous HSV-2 glycoprotein subunit vaccines have failed in clinical trials.

Purpose of the Study:

  • To review evidence supporting live HSV-2 vaccines.
  • To explore the potential of live HSV-2 vaccines in preventing genital herpes spread.
  • To address and contextualize safety concerns surrounding live HSV-2 vaccine development.

Main Methods:

  • Literature review of existing evidence on HSV-2 vaccines.
  • Comparative analysis of subunit versus live viral vaccine strategies.
  • Examination of historical safety data and regulatory hurdles for live HSV-2 vaccines.

Main Results:

  • Single-protein subunit vaccines represent a limited portion of HSV-2's antigenic breadth (approx. 1%).
  • Live HSV-2 vaccines expressing a vast majority of viral antigens (approx. 99%) show greater potential efficacy.
  • Clinical trial failures of subunit vaccines highlight limitations in antigenic coverage.

Conclusions:

  • Live HSV-2 vaccines offer a more comprehensive antigenic approach compared to subunit vaccines.
  • The broad antigen expression of live HSV-2 vaccines presents a promising strategy to control genital herpes.
  • Re-evaluation of unfounded safety concerns is crucial for advancing live HSV-2 vaccines into clinical trials.