Abstract
Abstract Human cytogemalovirus (HCMV) causes wide-spread infection in adult human populations. Although no symptoms observed in healthy persons, HCMV infection can cause severe and even life-threatening diseases in immune-compromised individuals. There are lines of evidence that humoral immunity can provide protection against HCMV infection. We have tested several versions of HCMV vaccines based on laboratory strain AD169 with its epithelial tropism restored in rhesus macaques. Vaccines were administered intramuscularly three times. In comparison, recombinant HCMV gB protein vaccine, which showed marginal protections in previous clinical trial, was given with adjuvant MF59. To facilitate the evaluation of these vaccines, we have developed a novel micro-neutralization assay based on the detection of a dominant HCMV antigen expressed in ARPE19 cells, using near infrared dye-labeled immune reagents, to measure HCMV neutralizing activities in serum samples of vaccinated monkeys. Our results showed that AD169 revertant vaccines induced much stronger neutralizing activities than recombinant gB vaccine in rhesus monkeys. The addition of ISCOMATRIX adjuvant (CSL, Ltd) in the vaccine formulation further enhanced its immunogenicity. There were significant boost effects after the second injection, while the third injection did not increase the neutralizing titers above those obtained post the second vaccination.
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