Development of a cytomegalovirus vaccine lessons from recent clinical trials

Eva Gonczol, Stanley Plotkin

Research output: Article

66 Citations (Scopus)

Abstract

Cytomegalovims-caused diseases are preventable. We believe that both neutralising antibodies and cell-mediated immunity are necessary for prevention. Of the CMV proteins, gB and pp65 are the minimum requirements in a vaccine to induce neutralising antibodies and cytotoxic T-lymphocyte (CTL) responses. Immunisation with additional proteins, e.g., gH, gN for neutralising antibodies and lElexon 4 and pp!50 for CTL responses, would strengthen protective immune responses. Approaches to development of a safe and effective cytomegalovirus (CMV) vaccine for the prevention of CMV diseases include a) a live attenuated vaccine (Towne strain); b) recombinant constructs of the attenuated Towne and the virulent Toledo CMV strains; c) subunit glycoprotein B (gB) adjuvanted with MF59 to induce neutralising antibodies; d) phosphoprotein 65 (pp65) peptidebased vaccines to induce (CTL) for use in therapeutic vaccination; e) canarypox-CMV recombinants, e.g., ALVAC-CMV(gB) and ALVAC-CMV (pp65) to induce neutralising antibodies and CTL responses, respectively; 0 DNA plasmids containing the genes for gB and pp65; g) dense bodies containing the key antigens. The attenuated Towne strain, gB/MF59, ALVAC-CMV(gB) and ALVAC-CMV(pp65) approaches have already been tested in clinical trials. The Towne vaccine induced neutralising antibodies and cell-mediated immunity (including CTLs) mitigated CMV disease in seronegative renal transplant recipients and protected against a low-dose virulent CMV challenge in normal volunteers but did not prevent infection in mothers of children excreting CMV. Immunisation with gB/MF59 resulted in high levels of neutralising antibodies in seronegative subjects. ALVAC-CMV(gB) did not induce neutralising antibodies but primed the immune system to a Towne strain challenge, while ALVAC-CMV(pp65) induced long-lasting CTL responses in all originally seronegative volunteers, with CTL precursor frequency similar to naturally seropositive individuals. These results suggest that CMV diseases can be prevented or attenuated and that a vaccine combining ALVAC-CMV(pp65) with gB/MF59 may induce sufficient CTLs and neutralising antibodies to protect against CMV diseases. Meanwhile, other approaches such as DNA peptide and dense body vaccines, should enter Phase I trials. All candidate vaccines will have to demonstrate that immunogenicity provides protection. Combined vaccines containing canarypox (ALVAC) vectors to express CMV-pp65 to induce CTLs and of subunit gB, given together with an appropriate adjuvant to induce neutralising antibodies, should be tested in a target population for the prevention of CMV infection and disease. 2001

Original languageEnglish
Pages (from-to)401-412
Number of pages12
JournalExpert Opinion on Biological Therapy
Volume1
Issue number3
DOIs
Publication statusPublished - jan. 1 2001

    Fingerprint

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this