Immunogenicity and Protective Efficacy of Recombinant Human T-Cell Leukemia/Lymphoma Virus Type 1 NYVAC and Naked DNA Vaccine Candidates in Squirrel Monkeys (Saimiri sciureus)

Abstract

We assessed the immunogenicities and efficacies of two highly attenuated vaccinia virus-derived NYVAC vaccine candidates encoding the human T-cell leukemia/lymphoma virus type 1 (HTLV-1) env gene or both the env and gag genes in prime-boost pilot regimens in combination with naked DNA expressing the HTLV-1 envelope. Three inoculations of NYVAC HTLV-1 env at 0, 1, and 3 months followed by a single inoculation of DNA env at 9 months protected against intravenous challenge with HTLV-1-infected cells in one of three immunized squirrel monkeys. Furthermore, humoral and cell-mediated immune responses against HTLV-1 Env could be detected in this protected animal. However, priming the animal with a single dose of env DNA, followed by immunization with the NYVAC HTLV-1 gag and env vaccine at 6, 7, and 8 months, protected all three animals against challenge with HTLV-1-infected cells. With this protocol, antibodies against HTLV-1 Env and cell-mediated responses against Env and Gag could also be detected in the protected animals. Although the relative superiority of a DNA prime-NYVAC boost regimen over addition of the Gag component as an immunogen cannot be assessed directly, our findings nevertheless show that an HTLV-1 vaccine approach is feasible and deserves further study.

Molecular and cellular aspects of HTLV-1 associated leukemogenesis in vivo

“…Analyzing the HTLV-1 replication pattern over time in PBMCs and various organs from HTLV-1 experimentally infected monkeys revealed that PBMCs and lymphoid organs constitute the major reservoirs for HTLV-1. [50][51][52][53] A pattern of persistent clonal expansion of infected cells, identical to that observed in humans, was evidenced in the PBMCs of experimentally infected animals. 51 The dissemination of the virus throughout the different body compartments appeared to result from the cellular transport of the integrated provirus.…”

Animal models for human T-lymphotropic virus type 1 (HTLV-1) infection and transformation

“…Subsequently, successful passive immunization has been achieved with hyperimmune globulin from healthy donors (Murata et al, 1996;Akari et al, 1997). Successful immunization against HTLV-1 infection has also been accomplished with recombinant vaccinia virus expressing envelope or gag gene products in combination with DNA vaccines (Ibuki et al, 1997;Kazanji et al, 2001). …”

“…Nonhuman primates have been infected with HTLV-1 and certain species have a natural infection with simian T-lymphotropic virus infection type 1 (STLV-1) (Gessain and Dethe 1996;Takemura et al, 2002;Gabet et al, 2003). The squirrel monkey has been successfully infected with HTLV-1 and offers an attractive nonhuman primate model of HTLV-1 for vaccine testing (Kazanji, 2000;Kazanji et al, 2001;Mortreux et al, 2001a;Sundaram et al, 2004). Rats have been infected with HTLV-1-producing cells and offer a tractable model of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/ATL), the neurologic disease associated with the viral infection (Suga et al, 1991;Ishiguro et al, 1992;Kasai et al, 1999;Sun et al, 1999;Kannagi et al, 2000;Hakata et al, 2001).…”

Clonagem e expressão da glicoproteína transmembrana do retrovírus HTLV-1 em células de mamíferos

“…Além de usarem diferentes sistemas de expressão, estes trabalhos também diferem quanto a utilização dos produtos recombinantes; as glicoproteínas do envelope do HTLV-1 podem ser incorporadas às reações bioquímicas in vitro, com o objetivo de estudar a formação de sincícios e a entrada do vírus nas células alvo 4 , podem ser utilizadas no diagnóstico da infecção pelo HTLV-1 11 ou podem ser utilizadas em protocolos de imunização experimental de animais, com o objetivo de produzir uma vacina recombinante contra o vírus 9 .…”