Adjuvant-like effect of vaccinia virus 14K protein: a case study with malaria vaccine based on the circumsporozoite protein

Aneesh Vijayan; Carmen E Gómez; Diego A Espinosa; Alan G Goodman; Lucas Sanchez-Sampedro; Carlos Oscar S Sorzano; Fidel Zavala; Mariano Esteban

doi:10.4049/jimmunol.1102492

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Adjuvant-like effect of vaccinia virus 14K protein: a case study with malaria vaccine based on the circumsporozoite protein

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Adjuvant-like effect of vaccinia virus 14K protein: a case study with malaria vaccine based on the circumsporozoite protein

Aneesh Vijayan, Carmen E Gómez, Diego A Espinosa, Alan G Goodman, Lucas Sanchez-Sampedro, Carlos Oscar S Sorzano, Fidel Zavala and Mariano Esteban

The Journal of immunology (1950), Vol.188(12), pp.6407-6417

06/15/2012

DOI: https://doi.org/10.4049/jimmunol.1102492

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https://hdl.handle.net/2376/104676

PMCID: PMC4181723

PMID: 22615208

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Abstract

Recombinant Fusion Proteins - immunology

Adjuvants, Immunologic - pharmacology

Antigens, Protozoan - immunology

Enzyme-Linked Immunosorbent Assay

Humans

Malaria - immunology

Viral Proteins - immunology

Reverse Transcriptase Polymerase Chain Reaction

Malaria Vaccines - chemical synthesis

Vaccinia virus - immunology

Malaria - prevention & control

Microscopy, Confocal

Animals

Malaria Vaccines - immunology

Mice

Mice, Inbred BALB C

Protozoan Proteins - immunology

Flow Cytometry

Development of subunit vaccines for malaria that elicit a strong, long-term memory response is an intensive area of research, with the focus on improving the immunogenicity of a circumsporozoite (CS) protein-based vaccine. In this study, we found that a chimeric protein, formed by fusing vaccinia virus protein 14K (A27) to the CS of Plasmodium yoelii, induces strong effector memory CD8(+) T cell responses in addition to high-affinity Abs when used as a priming agent in the absence of any adjuvant, followed by an attenuated vaccinia virus boost expressing CS in murine models. Moreover, priming with the chimeric protein improved the magnitude and polyfunctionality of cytokine-secreting CD8(+) T cells. This fusion protein formed oligomers/aggregates that led to activation of STAT-1 and IFN regulatory factor-3 in human macrophages, indicating a type I IFN response, resulting in NO, IL-12, and IL-6 induction. Furthermore, this vaccination regimen inhibited the liver stage development of the parasite, resulting in sterile protection. In summary, we propose a novel approach in designing CS based pre-erythrocytic vaccines against Plasmodium using the adjuvant-like effect of the immunogenic vaccinia virus protein 14K.

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Title: Adjuvant-like effect of vaccinia virus 14K protein: a case study with malaria vaccine based on the circumsporozoite protein
Creators: Aneesh Vijayan - Departamento de Biología Celular y Molecular, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas, 28049 Madrid, Spain
Carmen E Gómez
Diego A Espinosa
Alan G Goodman
Lucas Sanchez-Sampedro
Carlos Oscar S Sorzano
Fidel Zavala
Mariano Esteban
Publication Details: The Journal of immunology (1950), Vol.188(12), pp.6407-6417
Academic Unit: School of Molecular Biosciences
Publisher: United States
Grant note: AI44375 / NIAID NIH HHS R21 AI044375 / NIAID NIH HHS R01 AI044375 / NIAID NIH HHS
Identifiers: 99900547091801842
Language: English
Resource Type: Accepted manuscript