Immunization with recombinant adenovirus synthesizing the secretory form of Japanese encephalitis virus envelope protein protects adenovirus-exposed mice against lethal encephalitis (original) (raw)
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Journal of Immunology, 1988
We have identified and characterized nine antigenic epitopes on the E envelope of Japanese encephalitis virus (JEV) by using mAb. Passive administration of most of the anti-JEV mAb protected mice from i.v. challenge with 1.5 x lo3 plaque-formin$ units of JEV, JaGAr-01 strain. Some mAb, which possess high neutralization activity in vitro, showed high protection, and JEV-specific N mAb 503 was found the most protective. Even an injection of 2.5 &mouse of mAb 503 protected all mice from JEV infection. Furthermore, an injection of about 200 pg of mAb 503 on day 5 postinfection protected 82% of the mice, even when JEV was detected in more than 85% of the infected mouse brains. Synergism of protection was observed with mixtures of several mAb directed against different epitopes. Although in a murine macrophage cell line, all of the mAb groups showed antibody-dependent enhancement (ADE) of JEV infectivity in vitro, and only two flavivirus cross-reactive mAb groups showed ADE of dengue virus type 2. The ADE of JEV by mAb seems not to be harmful for in vivo protection experiments, except for two mAb groups: mAb 302 and 201 showed little or no protective activity against JEV infection and, rather, caused early death in infected mice.
Vaccine, 2011
Different subsets of dendritic cells (DC) elicit qualitatively different immune responses. In mice, two lymphoid tissue-resident subsets, CD8␣ + and CD8␣ − , have been implicated in the induction of T helper 1 (Th1) or Th2 responses, respectively. Moreover, CD8␣ + DC appear to play a major role in priming CD8 + T lymphocyte responses to viral antigens in the course of diverse viral infections. These considerations have been less extensively explored for vaccine vectors derived from viruses. Despite inefficient ex vivo transduction of DC, vectored vaccines derived from human adenoviruses of serotype 5 (Ad5) elicit robust immune responses, predominantly of the Th1 orientation, in humans and mice. At present it is unknown whether Ad5 interacts with DC subsets in a differential manner, thereby influencing the quality of the elicited IR. To address this issue, successive steps (attachment, transgene expression, MHC class I antigen presentation and activation of antigen-specific T lymphocytes) involved in induction of immune responses by Ad5-based vectors have been examined in CD8␣ + and CD8␣ − murine DC subsets. Although in both ex vivo and in vivo experiments CD8␣ + and CD8␣ − DC subsets captured an Ad5-based vector to a similar extent, transgene expression and subsequent MHC class I display of a transgene-encoded antigen were more efficient in CD8␣ + DC. Moreover, following in vivo and ex vivo transduction with an Ad5based vaccine, antigen-specific CD8 + T lymphocytes were more efficiently activated by CD8␣ + DC than by CD8␣ − DC. Thus, superior antigen expression and MHC class I display in CD8␣ + DC may contribute to preferred priming of antigen-specific CD8 + lymphocytes by Ad5-transduced CD8␣ + DC.
Journal of Virology, 2004
The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. Ad5-specific neutralizing antibodies (NAbs) are thought to contribute substantially to anti-Ad5 immunity, but the potential importance of Ad5-specific T lymphocytes in this setting has not been fully characterized. Here we assess the relative contributions of Ad5-specific humoral and cellular immune responses in blunting the immunogenicity of a rAd5-Env vaccine in mice. Adoptive transfer of Ad5-specific NAbs resulted in a dramatic abrogation of Env-specific immune responses following immunization with rAd5-Env. Interestingly, adoptive transfer of Ad5-specific CD8 + T lymphocytes also resulted in a significant and durable suppression of rAd5-Env immunogenicity. These data demonstrate that NAbs and CD8 + T lymphocytes both contribute...
Vaccine, 2009
Japanese encephalitis is a major cause of encephalitis in Asia. Cases occur largely in rural areas of the South and East Asian region resulting in significant morbidity and mortality. Multiple vaccines exist to control Japanese encephalitis, but all suffer from problems. Envelope protein domain III of Japanese encephalitis virus is involved in binding to host receptors and it contains specific epitopes that elicit virusneutralizing antibodies. Earlier, the protective efficacy of domain III has been evaluated in mice by some researchers, but these studies are lacking in explanation of humoral and cellular immune responses. We have earlier reported cloning, expression, purification and in vitro refolding of Japanese encephalitis virus envelope protein domain III (rJEV-DIII). Ninety percent JEV is neutralized when the serum against refolded rJEV-DIII is used at a dilution of 1:80. In the present study, we have evaluated the immunomodulatory potential of refolded rJEV-DIII protein in BALB/c mice with Freunds complete/incomplete adjuvants. Mice were tested for humoral immune response by ELISA. Cell-mediated immune response was tested by lymphocyte proliferation assay and cytokine profiling. The rJEV-DIII generated high IgG antibody and its isotypes (IgG2a and IgG3) and induced significant expression of INF-␥ and IL-2 cytokines. The rJEV-DIII induced significant lymphoproliferation of splenocytes. In conclusion rJEV-DIII induced Th1 type of immune response which plays an important role in protection for intracellular pathogens.
Host Defence Mechanisms Against Japanese Encephalitis Virus Infection in Mice
Journal of General Virology, 1983
The role of antibody and cell-mediated immunity in the resistance to Japanese encephalitis virus (JEV) infection was studied in adult mice. Passively transferred antibodies obtained up to 2 weeks after primary infection protected the recipient mice against a challenge infection with JEV. Antibody obtained at 4 or 5 weeks failed to protect despite the presence of high titres of neutralizing antibody. Protection was abrogated by pretreatment of the early serum with 2-mercaptoethanol to remove ]gM. Similarly, adoptive transfer of immune spleen cells obtained up to 2 weeks after immunization provided protection. The protective effect was abolished by pretreatment of the immune spleen cells with anti-Thy 1.2 antiserum and complement. These findings suggest a role of T lymphocytes and IgM antibody in recovery from JEV infection.
Vaccine, 1999
Genes encoding the glycosylated precursor of the membrane (prM) and envelope (E) proteins of a Korean strain of Japanese encephalitis virus (JEV) were inserted into the genome of the host-range restricted, highly attenuated, and safety-tested MVA strain of vaccinia virus. MVA recombinants containing the JEV genes, under strong synthetic or modi®ed H5 vaccinia virus promoters, were isolated. Synthesis of JEV prM and E proteins was detected by immuno¯uorescence microscopy,¯ow cytometry, and polyacrylamide gel electrophoresis. Mice inoculated and boosted by various routes with either of the MVA recombinants produced JEV neutralizing antibodies, that had titres comparable with those induced by an inactivated JEV vaccine, as well as haemagglutination-inhibiting antibodies. Mice immunized with 2 Â 10 6 infectious units of MVA/JEV recombinants by intramuscular or intraperitoneal routes were completely protected against a 10 5 LD 50 JEV challenge at 9 weeks of age. #
Journal of General Virology, 2010
Advax is a polysaccharide-based adjuvant that potently stimulates vaccine immunogenicity without the increased reactogenicity seen with other adjuvants. This study investigated the immunogenicity of a novel Advax-adjuvanted Vero cell culture candidate vaccine against Japanese encephalitis virus (JEV) in mice and horses. The results showed that, in mice, a two-immunization, low-dose (50 ng JEV antigen) regimen with adjuvanted vaccine produced solid neutralizing immunity comparable to that elicited with live ChimeriVax-JE immunization and superior to that elicited with tenfold higher doses of a traditional non-adjuvanted JEV vaccine (JE-VAX; Biken Institute) or a newly approved alum-adjuvanted vaccine (Jespect; Novartis). Mice vaccinated with the Advax-adjuvanted, but not the unadjuvanted vaccine, were protected against live JEV challenge. Equine immunizations against JEV with Advax-formulated vaccine similarly showed enhanced vaccine immunogenicity, confirming that the adjuvant effects of Advax are not restricted to rodent models. Advax-adjuvanted JEV vaccine elicited a balanced T-helper 1 (Th1)/Th2 immune response against JEV with protective levels of cross-neutralizing antibody against other viruses belonging to the JEV serocomplex, including Murray Valley encephalitis virus (MVEV). The adjuvanted JEV vaccine was well tolerated with minimal reactogenicity and no systemic toxicity in immunized animals. The cessation of manufacture of traditional mouse brain-derived unadjuvanted JEV vaccine in Japan has resulted in a JEV vaccine shortage internationally. There is also an ongoing lack of human vaccines against other JEV serocomplex flaviviruses, such as MVEV, making this adjuvanted, cell culture-grown JEV vaccine a promising candidate to address both needs with one vaccine.
Virology, 1991
Immunization with recombinant vaccinia viruses that specified the synthesis of Japanese encephalitis virus (JEV) glycoproteins protected mice from a lethal intraperitoneal challenge with JEV. Recombinants which coexpressed the genes for the structural glycoproteins, prM and E, elicited high levels of neutralizing (NEUT) and hemagglutination inhibiting (HAI) antibodies in mice and protected mice from a lethal challenge by JEV. Recombinants expressing only the gene for the nonstructural glycoprotein, NS1, induced antibodies to NS1 but provided low levels of protection from a similar challenge dose of JEV. Antibodies to the NS3 protein in postchallenge sera, representing the degree of infection with challenge virus, were inversely correlated to NEUT and HAI titers and levels of protection. These results indicate that although vaccinia recombinants expressing NS1 can provide some protection from lethal JEV infection, recombinants expressing prM and E elicited higher levels of protective...
The Journal of Immunology, 2004
The high prevalence of pre-existing immunity to adenovirus serotype 5 (Ad5) in human populations may substantially limit the immunogenicity and clinical utility of recombinant Ad5 vector-based vaccines for HIV-1 and other pathogens. A potential solution to this problem is to use vaccine vectors derived from adenovirus (Ad) serotypes that are rare in humans, such as Ad35. However, cross-reactive immune responses between heterologous Ad serotypes have been described and could prove a major limitation of this strategy. In particular, the extent of immunologic cross-reactivity between Ad5 and Ad35 has not previously been determined. In this study we investigate the impact of pre-existing anti-Ad5 immunity on the immunogenicity of candidate rAd5 and rAd35 vaccines expressing SIV Gag in mice. Anti-Ad5 immunity at levels typically found in humans dramatically blunted the immunogenicity of rAd5-Gag. In contrast, even high levels of anti-Ad5 immunity did not substantially suppress Gag-specif...