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Cytomegalovirus vaccines fail to induce epithelial entry neutralizing antibodies comparable to natural infection

Xiaohong Cui1, Benjamin P Meza, Stuart P Adler

  • 1Department of Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, VA 23298-0163, USA.

Vaccine
|August 23, 2008
PubMed

Insights

Natural cytomegalovirus (CMV) infections generate antibodies that are highly effective against epithelial cell entry, unlike fibroblast entry. Enhancing vaccine strategies to target these specific antibodies may improve CMV vaccine efficacy.

Area of Science:

  • Virology
  • Immunology
  • Vaccinology

Background:

  • Cytomegalovirus (CMV) entry mechanisms differ between cell types, notably fibroblasts versus epithelial and endothelial cells.
  • Antibodies neutralizing CMV fibroblast entry primarily target virion glycoproteins essential for attachment and entry.

Purpose of the Study:

  • To investigate the neutralizing antibody activity against CMV entry into epithelial cells compared to fibroblasts.
  • To evaluate the specificity of neutralizing antibodies induced by natural infection and CMV vaccines.

Main Methods:

  • Simultaneous measurement of neutralizing activities against CMV entry into fibroblasts and epithelial cells.
  • Analysis of human immune sera, CMV-hyperimmuneglobulins, Towne vaccine, and gB/MF59 subunit vaccine responses.
  • Adsorption assays using recombinant gB to assess antibody epitope specificity.

Main Results:

  • Human immune sera and CMV-hyperimmuneglobulins exhibited significantly higher neutralizing activity (48-fold average) against epithelial cell entry than fibroblast entry.
  • Natural CMV infections induce potent, epithelial entry-specific neutralizing antibodies, not adsorbed by recombinant gB.
  • The Towne and gB/MF59 vaccines induced lower levels of epithelial entry-specific neutralizing activity compared to natural infection (28-fold and 15-fold lower, respectively).

Conclusions:

  • Natural CMV infection elicits neutralizing antibodies with a strong preference for epithelial cell entry.
  • Current CMV vaccines (Towne and gB/MF59) induce less potent epithelial entry-specific neutralizing antibodies compared to natural infection.
  • CMV vaccine efficacy could potentially be improved by focusing on the induction of epithelial entry-specific neutralizing antibodies.

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