Construction of Oka varicella vaccine expressing human immunodeficiency virus env antigen

Abstract

Oka varicella vaccine has been used to confer active immunity to varicella-zoster virus (VZV) in healthy and immunocompromised hosts. Based on its attenuated nature, Oka varicella vaccine expressing human immunodeficiency virus (HIV) env antigen was constructed by inserting the HIVenv gene into the viral genome and its immunogenicity was assessed in guinea pigs. The HIVenv gene encoding 296-463 amino acids was inserted between the sequences of the hepatitis B surface antigen and the thymidine kinase gene of the cloned plasmid and the recombinant virus was isolated by cotransfection of the chimeric plasmid with viral DNA. Insertion of the HIVenv gene into the viral genome was confirmed by PCR and sequencing of the viral genome of the recombinant virus. The recombinant virus expressed 30k HIVenv fusion protein in its infected cells. In guinea pigs, immunization with the recombinant virus induced an antibody response to both the HIV antigen and the V3 peptide of gp120 as well as VZV gE:gI. Cell-mediated immunity to the HIV antigen and gE:gI was assessed by the cutaneous reaction representing delayed type hypersensitivity. Immunized guinea pigs responded well to both the HIV antigen and gE:gI. Thus the recombinant Oka varicella vaccine expressing the HIVenv antigen induced both a humoral and cell-mediated immunity to the HIV antigen similar to VZV as Oka varicella vaccine induces humoral and cell-mediated immunity to VZV in the vaccinees. This recombinant Oka varicella vaccine expressing the HIVenv antigen may be evaluated for its immunogenicity as one of the AIDS vaccine candidates.

The Varicella-Zoster Virus Open Reading Frame 63 Latency-Associated Protein Is Critical for Establishment of Latency

“…A live VZV vaccine in which ORF63 has been deleted could have advantages over the present vaccine, in that it might induce the strong immune responses associated with the live Oka vaccine strain but should be less likely to establish latency and therefore to reactivate and cause herpes zoster. Such a vaccine might also be useful to deliver other viral antigens to the immune system (7,31). Deletion of nearly the entire ORF63 gene markedly reduced latent infection, but the mutant virus grew to a peak titer that was lower than that of the parental virus.…”

Expression of Human Immunodeficiency Virus Type 1 gp120 from Herpes Simplex Virus Type 1-Derived Amplicons Results in Potent, Specific, and Durable Cellular and Humoral Immune Responses

“…Both herpes simplex virus type 1 (HSV-1) and varicella-zoster virus have been used for the expression of foreign genes, since these viruses can accommodate large segments of exogenous DNA with little effect on virus replication (15,43). Replication-competent and replication-defective gene replacement vectors based on both viruses are being explored as possible human immunodeficiency virus (HIV) vaccine delivery systems (32,45). The appeal of this approach lies in part in the ability of herpesviruses to (i) elicit strong cytotoxic-T-lymphocyte (CTL) responses; (ii) infect mucosal surfaces; (iii) infect a broad range of cell types, including dendritic cells (1,23,30,40); and (iv) establish a state of persistence in the infected cell.…”

Induction of humoral and cell-mediated immunity to hepatitis B surface antigen by a novel adjuvant activity of Oka varicella vaccine

“…VZV gE : gI was purified by the application of an Oka varicella vaccine-infected cell lysate to an affinity column coupled with a monoclonal antibody against gE (Kamiyama et al, 2000;Shiraki et al, 1997Shiraki et al, , 2001). Oka varicella vaccine was prepared from infected human embryonic lung cells (Kamiyama et al, 2000;Sato et al, 1998;Shiraki et al, 1984Shiraki et al, , 2001). The mock vaccine was prepared similarly but without infection.…”

“…HBsAg (1 mg) and gE : gI (1 mg) were used for the dose-finding experiment and HBsAg (2 mg) and gE : gI (3.2 mg) were used for the other experiments. The erythematous area was measured at 8, 24 and 48 h and the size (area) of the cutaneous reaction was determined at three sites at 24 h (Kamiyama et al, 2000;Sato et al, 1998;Shiraki et al, 2001). Sera were tested for antibody titres to gE : gI and HBsAg by ELISA (Kamiyama et al, 2000;Sato, 1998;Shiraki et al, 2001).…”

“…The erythematous area was measured at 8, 24 and 48 h and the size (area) of the cutaneous reaction was determined at three sites at 24 h (Kamiyama et al, 2000;Sato et al, 1998;Shiraki et al, 2001). Sera were tested for antibody titres to gE : gI and HBsAg by ELISA (Kamiyama et al, 2000;Sato, 1998;Shiraki et al, 2001). Sera were diluted 1 : 80 with PBS containing 2 % skimmed milk and applied to each well treated with 1 mg HBsAg and 0.5 mg gE : gI for antibody titres to HBsAg and gE : gI, respectively.…”