Development of replication-competent viral vectors for HIV vaccine delivery

Parks, Christopher L.; Picker, Louis J.; King, C. Richter

doi:10.1097/coh.0b013e328363d389

Cited by 57 publications

(34 citation statements)

References 119 publications

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“…These techniques target a specific PRR or a limited population of PRRs (32,34). However, activation of a broader range of PRRs resulting from release of damage-associated molecular patterns (DAMPs) during natural lytic viral infection is able to produce a more robust immune response (31,33,(35)(36)(37).…”

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confidence: 99%

“…The rationale of the present study was to develop DNA vaccines that mimic the effect of live attenuated virus (LAV) vaccines which, although attenuated, are still lytic, resulting in activation of cell death pathways that are considered important to generate robust immunity (36,37). Thus, the induction of necrosis in vaccine-targeted cells is expected to release the HCV immunogen and DAMPs, creating an adjuvant-rich milieu to enhance the HCV-specific immune responses after DNA immunization.…”

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confidence: 99%

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A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice

Gummow

et al. 2015

J Virol

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There are 3 to 4 million new hepatitis C virus (HCV) infections annually around the world, but no vaccine is available. Robust T-cell mediated responses are necessary for effective clearance of the virus, and DNA vaccines result in a cell-mediated bias. Adjuvants are often required for effective vaccination, but during natural lytic viral infections damage-associated molecular patterns (DAMPs) are released, which act as natural adjuvants. Hence, a vaccine that induces cell necrosis and releases DAMPs will result in cell-mediated immunity (CMI), similar to that resulting from natural lytic viral infection. We have generated a DNA vaccine with the ability to elicit strong CMI against the HCV nonstructural (NS) proteins (3, 4A, 4B, and 5B) by encoding a cytolytic protein, perforin (PRF), and the antigens on a single plasmid. We examined the efficacy of the vaccines in C57BL/6 mice, as determined by gamma interferon enzyme-linked immunosorbent spot assay, cell proliferation studies, and intracellular cytokine production. Initially, we showed that encoding the NS4A protein in a vaccine which encoded only NS3 reduced the immunogenicity of NS3, whereas including PRF increased NS3 immunogenicity. In contrast, the inclusion of NS4A increased the immunogenicity of the NS3, NS4B, andNS5B proteins, when encoded in a DNA vaccine that also encoded PRF. Finally, vaccines that also encoded PRF elicited similar levels of CMI against each protein after vaccination with DNA encoding NS3, NS4A, NS4B, and NS5B compared to mice vaccinated with DNA encoding only NS3 or NS4B/5B. Thus, we have developed a promising "multiantigen" vaccine that elicits robust CMI. IMPORTANCESince their development, vaccines have reduced the global burden of disease. One strategy for vaccine development is to use commercially viable DNA technology, which has the potential to generate robust immune responses. Hepatitis C virus causes chronic liver infection and is a leading cause of liver cancer. To date, no vaccine is currently available, and treatment is costly and often results in side effects, limiting the number of patients who are treated. Despite recent advances in treatment, prevention remains the key to efficient control and elimination of this virus. Here, we describe a novel DNA vaccine against hepatitis C virus that is capable of inducing robust cell-mediated immune responses in mice and is a promising vaccine candidate for humans. G lobal efforts to generate an effective vaccine for hepatitis C virus (HCV) have been hampered, since correlates of sterilizing immunity have not been identified and traditional vaccine strategies have proved to be ineffective (1). Approximately 230 million individuals are infected, many of whom will develop serious liver disease, and since current treatment is costly and often results in serious side effects, this has limited the number of patients who are treated (2, 3). Much of the global effort to develop an effective HCV vaccine/treatment has been directed toward genotype 1 (gt1) (4, 5); however, gt3 is ...

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A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice

Gummow

et al. 2015

J Virol

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“…Challenges faced by vaccinologists include the genetic diversity of HIV, our lack of understanding of protective immunity (since there is no case of natural clearance of infection), the establishment of viral reservoirs that cannot be eliminated with antiretroviral therapy, and our inability to induce B cells making specific neutralizing antibodies (Picker et al 2012). Various types of immunogens (proteins, peptides, nucleic acids), viral vectors (non-replicative or attenuated persistent), vector-less system (nanoparticles carrying immunogen), and adjuvants are being tested in cellular studies, preclinical studies in animals, or in clinical trials (Johnson et al 2013;Parks et al 2013). The most encouraging results in recent preclinical studies used either chimeric SIV immunogens expressed by an adenoviral vector or an attenuated rhesus CMV viral vector expressing complete SIV proteins (Hansen et al 2013).…”

Section: Hiv Antigen Processing and Vaccine Immunogen Designmentioning

confidence: 99%

HIV Antigen Processing and Presentation

Boucau¹,

Ručević²,

Gall³

2014

Encyclopedia of AIDS

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“…Viral vectors have proven to be well tolerated and immunogenic with evidence of efficacy in macaques (Parks et al, 2013). Another strategy is the bacterial vectors used to express HIV antigens to induce immunity (Charbit et al, 1993;Sirois et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Expression of two loopsV3 from HIV-1 fused to cholera toxin A2B subunit using Lactococcus lactis as a vector to induce immunity in mucosa

Luna-Cruz¹,

Franco‐Molina²,

Rodríguez‐Padilla³

et al. 2014

Afr. J. Microbiol. Res.

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Lactococcus lactis, a nonpathogenic bacterium has been used widely as a vector to deliver antigens to the mucosa; one of the principal threats to world health is AIDS and HIV infection, involving the passage of the virus across a mucosal surface. We used L. lactis to express V3 loop from HIV-1, A2B subunit of cholera toxin and their fusion with one or two loops V3 (V3A2B and V3V3A2B). Six-weeks-old Balb/c mice were orally immunized with the recombinant bacteria. Samples of serum, intestinal washes and PBMC lymphocytes were collected to detect IgA and IgG anti-V3, and IL-2 respectively. The recombinants that express the V3 alone or fused to the A2B induced anti-V3 IgA antibodies and anti-V3 IgG antibodies in serum and intestinal washes but recombinant V3V3A2B was the most efficient and the only one that induced the expression of IL-2 in PBMC when compared with the controls (p<0.05). We induced anti V3 IgG and IgA and IL-2 in mice immunized with L. lactis recombinants that express the antigen V3 fused to A2B subunit of CT; which suggests that this strategy could be used to induce immune response specific of HIV.

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Development of replication-competent viral vectors for HIV vaccine delivery

Cited by 57 publications

References 119 publications

A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice

A Multiantigenic DNA Vaccine That Induces Broad Hepatitis C Virus-Specific T-Cell Responses in Mice

HIV Antigen Processing and Presentation

Expression of two loopsV3 from HIV-1 fused to cholera toxin A2B subunit using Lactococcus lactis as a vector to induce immunity in mucosa

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