Chimeras between the human immunodeficiency virus (HIV-1) Env and vaccinia virus immunogenic proteins p14 and p39 generate in mice broadly reactive antibodies and specific activation of CD8+ T cell responses to Env

Collado, Manuel; Rodrı́guez, Dolores; Rodríguez, Juan; Vázquez, Isabel Ramos; Gonzalo, Rosa; Esteban, Mariano

doi:10.1016/s0264-410x(00)00112-2

Cited by 7 publications

(4 citation statements)

References 39 publications

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Section: Discussioncontrasting

confidence: 60%

“…VACV that expressed a fusion of the HIV envelope protein with VACV A27 or A4 protein resulted in a broader and more neutralizing anti-HIV antibody responses in mice [43]. In comparison to our current study, none of the A27 or A4 fusion proteins appeared to be displayed on the surface of the virion [43, 44]. VACV that expressed the fusion of HIV envelope or Gag protein with VACV B5 protein elicited better antibody or CD4 + T cell responses to the HIV antigens [45–47].…”

Section: Discussionmentioning

confidence: 99%

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Enhancement of immune response to an antigen delivered by vaccinia virus by displaying the antigen on the surface of intracellular mature virion

Embry¹,

Meng²,

Cantwell³

et al. 2011

Vaccine

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Vaccinia virus (VACV) is the vaccine for smallpox and a widely-used vaccine vector for infectious diseases and cancers. The majority of the antibodies elicited by live VACV vaccination respond to virion structural proteins, including many integral membrane proteins on the intracellular mature virion (MV). Here, we showed that antibody response to an exogenous antigen delivered by VACV was greatly enhanced by incorporating the antigen as an integral membrane protein of MV. We constructed recombinant VACV expressing a Y. pestis protective antigen, LcrV, unmodified or fused with either a signal peptide or with the transmembrane domain of VACV D8 protein (LcrV-TM). Electron microscopy showed that LcrV-TM was displayed on the surface of MV. Importantly, VACV expressing LcrV-TM elicited a significantly higher titer of anti-LcrV antibody in mice than viruses expressing other forms of LcrV. Only mice immunized with LcrV-TM-expressing VACV were protected from lethal Y. pestis and VACV WR challenges. Antigen engineering through fusion with D8 transmembrane domain may be broadly applicable for enhancing the immune response to antigens delivered by a VACV vector. The recombinant virus described here could also serve as the basis for developing a vaccine against both smallpox and plague.

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Section: Discussioncontrasting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Enhancement of immune response to an antigen delivered by vaccinia virus by displaying the antigen on the surface of intracellular mature virion

Embry¹,

Meng²,

Cantwell³

et al. 2011

Vaccine

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“…Studies have shown that fusing immunogenic epitopes of human immunodeficiency virus type 1 with major antigenic envelope proteins of VACV B5R, A27L and the core protein A4L elicits Abs with higher specificity and strong neutralizing activity Collado et al, 2000;Loewinger & Katz, 2002). We are exploring the potential of ORFV for vaccine development using the above approach.…”

Section: Discussionmentioning

confidence: 99%

Investigation of orf virus structure and morphogenesis using recombinants expressing FLAG-tagged envelope structural proteins: evidence for wrapped virus particles and egress from infected cells

Tan

Ueda

Mercer

et al. 2009

Journal of General Virology

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Orf virus (ORFV) is the type species of the genus Parapoxvirus, but little is known about the structure or morphogenesis of the virus. In contrast, the structure and morphogenesis of vaccinia virus (VACV) has been extensively studied. VACV has two main infectious forms, mature virion (MV) and extracellular virion (EV). The MV is wrapped by two additional membranes derived from the trans-Golgi to produce a wrapped virion (WV), the outermost of which is lost by cellular membrane fusion during viral egress to form the EV. Genome sequencing of ORFV has revealed that it has homologues of almost all of the VACV structural genes. Notable exceptions are A36R, K2L, A56R and B5R, which are associated with WV and EV envelopes. This study investigated the morphogenesis and structure of ORFV by fusing FLAG peptide to the structural proteins 10 kDa, F1L and ORF-110 to form recombinant viruses. 10 kDa and F1L are homologues of VACV A27L and H3L MV membrane proteins, whilst ORF-110 is homologous to VACV A34R, an EV membrane protein. Immunogold labelling of FLAG proteins on virus particles isolated from lysed cells showed that FLAG-F1L and FLAG-10 kDa were displayed on the surface of infectious particles, whereas ORF-110-FLAG could not be detected. Western blot analysis of solubilized recombinant ORF-110-FLAG particles revealed that ORF-110-FLAG was abundant and undergoes post-translational modification indicative of endoplasmic reticulum trafficking. Fluorescent microscopy confirmed the prediction that ORF-110-FLAG localized to the Golgi in virus-infected cells. Finally, immunogold labelling of EVs showed that ORF-110-FLAG became exposed on the surface of EV-like particles as a result of egress from the cell.

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“…In fact, chimeras between VACV proteins and HIV Env had shown enhanced B and T cell responses to HIV-1 antigens. 143 In this way, we have recently described a fusion protein based on the VACV A27 protein (14 kDa) fused together with the circumsporozoite protein of Plasmodium (CS-14K). This fusion protein forms stable oligomers, was produced in quantities as a soluble product in E. coli, have an adjuvant-like effect, and when administered to mice in the absence of adjuvant and in combination with MVA expressing the CS protein of P. yoelii (MVA-PyCS), induced sterile protection after challenge with sporozoites of P. yoelii.…”

mentioning

confidence: 99%

Enhancing poxvirus vectors vaccine immunogenicity

García-Arriaza

Esteban

2014

Human Vaccines & Immunotherapeutics

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A ttenuated recombinant poxvirus vectors expressing heterologous antigens from pathogens are currently at various stages in clinical trials with the aim to establish their efficacy. This is because these vectors have shown excellent safety profiles, significant immunogenicity against foreign expressed antigens and are able to induce protective immune responses. In view of the limited efficacy triggered by some poxvirus strains used in clinical trials (i.e, ALVAC in the RV144 phase III clinical trial for HIV), and of the restrictive replication capacity of the highly attenuated vectors like MVA and NYVAC, there is a consensus that further improvements of these vectors should be pursuit. In this review we considered several strategies that are currently being implemented, as well as new approaches, to improve the immunogenicity of the poxvirus vectors. This includes heterologous prime/ boost protocols, use of co-stimulatory molecules, deletion of viral immunomodulatory genes still present in the poxvirus genome, enhancing virus promoter strength, enhancing vector replication capacity, optimizing expression of foreign heterologous sequences, and the combined use of adjuvants. An optimized poxvirus vector triggering longlasting immunity with a high protective efficacy against a selective disease should be sought.

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Chimeras between the human immunodeficiency virus (HIV-1) Env and vaccinia virus immunogenic proteins p14 and p39 generate in mice broadly reactive antibodies and specific activation of CD8+ T cell responses to Env

Cited by 7 publications

References 39 publications

Enhancement of immune response to an antigen delivered by vaccinia virus by displaying the antigen on the surface of intracellular mature virion

Enhancement of immune response to an antigen delivered by vaccinia virus by displaying the antigen on the surface of intracellular mature virion

Investigation of orf virus structure and morphogenesis using recombinants expressing FLAG-tagged envelope structural proteins: evidence for wrapped virus particles and egress from infected cells

Enhancing poxvirus vectors vaccine immunogenicity

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