Vaccination of immunocompetent elderly subjects with a live attenuated Okastrain of varicella tester virus: a randomized, controlled, dose-response trial

After primary infection in childhood, varicella tester virus (VZV) remains latent in the dorsal route ganglia. Its reactivation later in life can lead to a tester episode. VZV-specific, T-cell-mediated immunity (VZV-CMI) is l ikely to be important in preventing symptomatic reactivation. As CMI declin es with age, a vaccine enhancing VZV-CMI might be effective in decreasing t he incidence or severity of tester in elderly subjects. A randomized, doubl e blind controlled trial assessing CMI responses of elderly subjects immuni zed with a live attenuated, VZV-Oka vaccine was conducted. Two hundred heal thy volunteers (55-75 years of age) received either a single injection of t he VZV vaccine (PMC), containing 3200 (Oka 3200), 8500 (Oka 8500), or 41,65 0 (Oka 41650) PFU of live VZV, or a pneumococcus vaccine control group (Pne umo 23(R). The immune response to VZV was assessed by measuring the T-celI response to VZV antigens, i.e. proliferation (stimulation index, SI), precu rsor cell frequency (PCF), cytokine secretion, and antibody titers. Six wee ks post-vaccination, VZV-specific SI (adjusted mean values) was significant ly greater (P < 0.0001) in the 3 vaccine groups (with SI = 5.6 for Oka 3200 ; SI = 5.0 for Oka 8500, and SI = 7.2 for Oka 41,650) than in the control g roup (SI = 2.9). The increase in PCF was striking, with 72.4, 91.2 and 85.1 precursors per million cells respectively in these 3 vaccine groups, vs 26 .3 in the control group. No significant IL-4 secretion was observed in any subject, whereas the presence of IFN-gamma secretion was found to correlate with good responder status. The increase of these CMI parameters did not d epend upon the titer of virus injected. Geometric mean titers of VZV antibo dies increased in all vaccine groups and remained unchanged in the control group. Nevertheless, no correlation between the antibody response and the c ell-mediated response was found. Live attenuated VZV vaccine caused a signi ficant increase in VZV-CMI in a healthy, elderly population. No relationshi p between vaccine dose and the intensity of the specific response was found . (C) 2000 Elsevier Science Ltd. All rights reserved.