A Canarypox Vector Expressing Cytomegalovirus (CMV) Glycoprotein B Primes for Antibody Responses to a Live Attenuated CMV Vaccine (Towne)

Abstract

To develop a vaccine against cytomegalovirus (CMV), a canarypox virus (ALVAC) expressing CMV glycoprotein (gB) was evaluated alone or in combination with a live, attenuated CMV vaccine (Towne). Three doses of 106.5 TCID50 of ALVAC-CMV(gB) induced very low neutralizing or ELISA antibodies in most seronegative adults. However, to determine whether ALVAC-CMV(gB) could prime for antibody responses, 20 seronegative adults randomly received either 106.8 TCID50 of ALVAC-CMV(gB) or 106.8 TCID50 of ALVAC-RG, expressing the rabies glycoprotein, administered at 0 and 1 month, with all subjects receiving a dose of 103.5 pfu of the Towne vaccine at 90 days. For subjects primed with ALVAC-CMV(gB), neutralizing titers and ELISA antibodies to CMV(gB) developed sooner, were much higher, and persisted longer than for subjects primed with ALVAC-RG. All vaccines were well tolerated. These results demonstrate that ALVAC-CMV(gB) primes the immune system and suggest a combined-vaccine strategy to induce potentially protective levels of neutralizing antibodies.

Evaluation of recombinant modified vaccinia Ankara virus-based rhesus cytomegalovirus vaccines in rhesus macaques

“…However, the results were not unprecedented. Other studies have shown that a recombinant canarypox expressing HCMV gB did not stimulate immune responses in vaccinated humans, despite expression both in vitro and in small animals (mice and guinea pigs) [1,10]. Comparable to our study, the canarypox construct did prime the immune system as demonstrated by the memory response generated after infection with the live attenuated Towne vaccine.…”

A DNA-Based Vaccine for the Prevention of Human Cytomegalovirus-Associated Diseases

“…Although infection was not prevented, a subgroup of vaccinated patients did exhibit less severe disease manifestations. 37,43 A nonreplicating canarypox vector encoding HCMV gB has been investigated in Phase I studies alone and in combination with recombinant gB, 44,45 and a canarypox vaccine encoding pp65 has also been studied. 46 The latter induced CTL, lymphoproliferation, and antibody responses in all seronegative recipients in these Phase I trials.…”

Optimization of CD4+ T Lymphocyte Response to Human Cytomegalovirus Nuclear IE1 Protein through Modifications of Both Size and Cellular Localization

“…Several strategies have been explored (5). Protection of women of childbearing age would require a vaccine essentially inducing strong Ab production directed toward envelope glycoproteins such as gB (7). Patients with persistent infection may benefit from vaccines eliciting T lymphocyte responses, as proposed by different studies using dense bodies (32), canarypox virus recombinant for pp65 (33), attenuated poxviruses (34), recombinant adeno-associated virus (35), pp65-derived immunodominant peptide (36), and a fusion IE1-pp65 protein (13).…”

“…The relationships between viral genes transcription, localization, function, and the promotion of humoral and cell-mediated immune responses is unclear. Envelope glycoproteins such as gB, which are expressed during the late kinetic phase of virus replication, have been described as potential vaccines targeting the Ab response (7). The immediate early protein IE1 and the major tegument protein pp65 (early/late kinetics) have been described as targets for both CD4 and CD8 lymphocyte responses (8 -14).…”