Adjuvant-like Effect of Vaccinia Virus 14K Protein: A Case Study with Malaria Vaccine Based on the Circumsporozoite Protein

Vijayan, Aneesh; Gómez, Carmen Elena; Espinosa, Diego A.; Goodman, Alan G.; Sánchez-Sampedro, Lucas; Sorzano, Carlos Óscar S.; Zavala, Fidel; Esteban, Mariano

doi:10.4049/jimmunol.1102492

Cited by 9 publications

(12 citation statements)

References 65 publications

(62 reference statements)

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“…A) pCMV-gp120 BX08 : Plasmid vector expressing the mammalian codon optimized gp120 of HIV-1 BX08 isolate from clade B, containing an artificial signal peptide for enhanced secretion of the protein; the gp120 encoding BX08 gene was kindly provided by Sanofi-Pasteur. B) pcDNA-gp120-14K : Plasmid expressing the mammalian codon optimized gp120 of HIV-1 BX08 isolate from clade B, fused to the VACV 14K protein (derived from A27L gene), was generated following a similar strategy to the one previously described [ 26 ]. C) pBJ5-GS-gp120-14K : The chimeric HIV-1 gp120-14K gene was cloned into pBJ5-GS plasmid, a kind gift from José Casasnovas (CNB-CSIC), which contains a glutamine synthetase minigene.…”

Section: Methodsmentioning

confidence: 99%

“…Antibodies present in the serum of immunized animals were determined using ELISA as previously described [ 26 , 33 , 37 ]. Human broadly neutralizing antibodies (bnAbs) PG9 (ARP3294), PG16 (ARP3293), b12 (EVA3065), VRC01 (ARP3291) and 2G12 (EVA3064) were obtained from the Centre for AIDS Reagents, NIBSC.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously described a procedure to generate oligomeric forms of the Plasmodium circumsporozoite (CS) protein after its fusion to the VACV 14K (derived from A27L gene) protein and its adjuvant-like effect in prime-boost immunization protocols conferring protection after challenge with the malaria parasite [ 26 ]. VACV 14K protein is composed of 110 amino acid (aa) residues containing a heparin binding domain (HBD), a coiled-coil domain (CCD) and a leucine zipper domain (LZD).…”

Section: Introductionmentioning

confidence: 99%

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A Chimeric HIV-1 gp120 Fused with Vaccinia Virus 14K (A27) Protein as an HIV Immunogen

et al. 2015

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In the HIV vaccine field, there is a need to produce highly immunogenic forms of the Env protein with the capacity to trigger broad B and T-cell responses. Here, we report the generation and characterization of a chimeric HIV-1 gp120 protein (termed gp120-14K) by fusing gp120 from clade B with the vaccinia virus (VACV) 14K oligomeric protein (derived from A27L gene). Stable CHO cell lines expressing HIV-1 gp120-14K protein were generated and the protein purified was characterized by size exclusion chromatography, electron microscopy and binding to anti-Env antibodies. These approaches indicate that gp120-14K protein is oligomeric and reacts with a wide spectrum of HIV-1 neutralizing antibodies. Furthermore, in human monocyte-derived dendritic cells (moDCs), gp120-14K protein upregulates the levels of several proinflammatory cytokines and chemokines associated with Th1 innate immune responses (IL-1β, IFN-γ, IL-6, IL-8, IL-12, RANTES). Moreover, we showed in a murine model, that a heterologous prime/boost immunization protocol consisting of a DNA prime with a plasmid expressing gp120-14K protein followed by a boost with MVA-B [a recombinant modified vaccinia virus Ankara (MVA) expressing HIV-1 gp120, Gag, Pol and Nef antigens from clade B], generates stronger, more polyfunctional, and greater effector memory HIV-1-specific CD4+ and CD8+ T-cell immune responses, than immunization with DNA-gp120/MVA-B. The DNA/MVA protocol was superior to immunization with the combination of protein/MVA and the latter was superior to a prime/boost of MVA/MVA or protein/protein. In addition, these immunization protocols enhanced antibody responses against gp120 of the class IgG2a and IgG3, together favoring a Th1 humoral immune response. These results demonstrate that fusing HIV-1 gp120 with VACV 14K forms an oligomeric protein which is highly antigenic as it activates a Th1 innate immune response in human moDCs, and in vaccinated mice triggers polyfunctional HIV-1-specific adaptive and memory T-cell immune responses, as well as humoral responses. This novel HIV-1 gp120-14K immunogen might be considered as an HIV vaccine candidate for broad T and B-cell immune responses.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Chimeric HIV-1 gp120 Fused with Vaccinia Virus 14K (A27) Protein as an HIV Immunogen

et al. 2015

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“…The most frequent example of this across different models is specific CD8 + T cells producing IFN-γ and TNF simultaneously. High frequencies of polyfunctional specific CD8 + T cells were described in (i) mice (Masopust et al, 2006; Duke et al, 2007; de Alencar et al, 2009; Elvang et al, 2009; Reyes-Sandoval et al, 2010; Rigato et al, 2011; Rodríguez et al, 2012; Vijayan et al, 2012), (ii) NHP (Mattapallil et al, 2006; Sun et al, 2006; Cox et al, 2008; Liu et al, 2008; Magalhaes et al, 2008; Cayabyab et al, 2009; Wilks et al, 2010; Hutnick et al, 2012), and (iii) humans (Beveridge et al, 2007; Harari et al, 2008; Winstone et al, 2009; Freel et al, 2010; Jaoko et al, 2010; Koup et al, 2010; Schooley et al, 2010; Churchyard et al, 2011; De Rosa et al, 2011). …”

Section: Characteristics Of Protective Cd8+ T Cells Elicited After Hementioning

confidence: 99%

Relevance of long-lived CD8+ T effector memory cells for protective immunity elicited by heterologous prime-boost vaccination

Vasconcelos¹,

Dominguez²,

Araújo³

et al. 2012

Front. Immun.

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Owing to the importance of major histocompatibility complex class Ia-restricted CD8+ T cells for host survival following viral, bacterial, fungal, or parasitic infection, it has become largely accepted that these cells should be considered in the design of a new generation of vaccines. For the past 20 years, solid evidence has been provided that the heterologous prime-boost regimen achieves the best results in terms of induction of long-lived protective CD8+ T cells against a variety of experimental infections. Although this regimen has often been used experimentally, as is the case for many vaccines, the mechanism behind the efficacy of this vaccination regimen is still largely unknown. The main purpose of this review is to examine the characteristics of the protective CD8+ T cells generated by this vaccination regimen. Part of its efficacy certainly relies on the generation and maintenance of large numbers of specific lymphocytes. Other specific characteristics may also be important, and studies on this direction have only recently been initiated. So far, the characterization of these protective, long-lived T cell populations suggests that there is a high frequency of polyfunctional T cells; these cells cover a large breadth and display a T effector memory (TEM) phenotype. These TEM cells are capable of proliferating after an infectious challenge and are highly refractory to apoptosis due to a control of the expression of pro-apoptotic receptors such as CD95. Also, they do not undergo significant long-term immunological erosion. Understanding the mechanisms that control the generation and maintenance of the protective activity of these long-lived TEM cells will certainly provide important insights into the physiology of CD8+ T cells and pave the way for the design of new or improved vaccines.

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“…The most frequent example of this across different models is specific CD8 + T cells producing IFN-γ and TNF simultaneously. High frequencies of polyfunctional specific CD8 + T cells were described in (i) mice (Masopust et al, 2006;Duke et al, 2007;Elvang et al, 2009;Reyes-Sandoval et al, 2010;Rodríguez et al, 2012;Vijayan et al, 2012), (ii) NHP (Mattapallil et al, 2006;Sun et al, 2006;Cox et al, 2008;Liu et al, 2008;Magalhaes et al, 2008;Cayabyab et al, 2009;Wilks et al, 2010;Hutnick et al, 2012), and (iii) humans (Beveridge et al, 2007;Harari et al, 2008;Winstone et al, 2009;Churchyard et al, 2011;De Rosa et al, 2011).…”

Section: Polyfunctionality Of Specific Cd8 + T Cellsmentioning

confidence: 99%

Importância da resposta aos epítopos subdominantes, da proliferação e da recirculação de linfócitos T CD8+ durante a vacinação experimental contra a infecção pelo Trypanosoma cruzi.

Dominguez¹

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Adjuvant-like Effect of Vaccinia Virus 14K Protein: A Case Study with Malaria Vaccine Based on the Circumsporozoite Protein

Cited by 9 publications

References 65 publications

A Chimeric HIV-1 gp120 Fused with Vaccinia Virus 14K (A27) Protein as an HIV Immunogen

A Chimeric HIV-1 gp120 Fused with Vaccinia Virus 14K (A27) Protein as an HIV Immunogen

Relevance of long-lived CD8+ T effector memory cells for protective immunity elicited by heterologous prime-boost vaccination

Importância da resposta aos epítopos subdominantes, da proliferação e da recirculação de linfócitos T CD8+ durante a vacinação experimental contra a infecção pelo Trypanosoma cruzi.

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