Immunogenicity of wild and attenuated varicella‐zoster virus strains in rhesus monkeys

Abstract

Thirty susceptible rhesus monkeys were inoculated with cell-free varicella-zoster virus strain OKA or strain KMcC. Both wild and attenuated strains were used. No clinical signs characteristic of human varicella were seen in any of the animals. Virus was not isolated from throat swabs, blood, or cerebrospinal fluid. Antibodies were measured by an enhanced plaque neutralization test. The wild and attenuated OKA strains produced comparable levels of antibodies for 3 months after inoculation. Attenuated KMcC strains produced lower titers than the wild strain. On rechallenge 3 months after primary inoculation animals boostered with the attenuated OKA strain developed significantly higher antibody titers than animals receiving the wild strain. Animals primed and challenged with the attenuated KMcC strains showed significantly lower antibody titers than animals which received the wild strain. The results indicate that the immunogenicity of attenuated OKA and KMcC strains in rhesus monkeys parallels the experience obtained with these strains in humans.

Abortive Intrabronchial Infection of Rhesus Macaques with Varicella-Zoster Virus Provides Partial Protection against Simian Varicella Virus Challenge

“…We were unable to measure amplification of VZV DNA at the site of inoculation, the lungs (via BAL sampling), or in the blood of rhesus macaques intrabronchially infected with VZV KMcC. Our results are similar to those of previous studies using (i) primary intratracheal and secondary intravenous inoculation of cynomolgus macaques with parental Oka strain (58), (ii) subcutaneous inoculation of rhesus macaques in both thighs with VZV OKA or KMcC (72), and (iii) intratracheal and subcutaneous inoculation with the CaQu or SPu strain of VZV in patas monkeys (57). Alternatively, following infection of common marmosets with VZV KMcC via a combined oral-nasal-conjunctival route, virus was detected in lung tissue by coculturing lung tissue from 6 to 7 days p.i.…”

“…Our current study sought to characterize disease progression, viral replication, immune response, and the establishment of latency in rhesus macaques following intrabronchial infection with wild-type VZV and subsequent challenge with SVV. In this initial study, we used the well-characterized wild-type VZV KMcC strain (56,69,72) in our rhesus macaque model. The current study sets the groundwork to evaluate novel vaccine strains and to assess the impact of alterations in the manufacture of vaccines on immunogenicity in future experiments.…”

“…In order to establish a robust animal model of varicella-zoster virus (VZV) infection, we chose the previously characterized wild-type (WT) strain KMcC at a low passage number (56,69,72,73). Four male rhesus macaques 4 to 5 years of age were infected intrabronchially with 1 ϫ 10 6 PFU of cell-associated WT VZV KMcC.…”

Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein

“…Early studies such as ref. 16 did not ascertain whether VZV-Oka replicated in RMs or whether it elicited cellular immune responses. To test the potential of VZV recombinants to serve as vectors for HIV vaccines, we inoculated RMs with the parental rVZV or rVZV-SIVenv expressing SIVsmH4 env (Fig.…”

“…RMs are not naturally infected with VZV, although VZV-Oka and clinical VZV isolates induce antibody titers in RMs that parallel those observed in humans (16). Early studies such as ref.…”