Antigen capsid-display on human adenovirus 35 via pIX fusion is a potent vaccine platform

Autor: Roland Zahn, Jan Serroyen, Esmeralda van der Helm, Hanneke Schuitemaker, Jerome Custers, Marija Vujadinovic, Lars Vorthoren, Nadine C. Salisch, Harmjan Kuipers, Jort Vellinga, Dirk Spek
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Humoral Immune Response
Physiology
Antibody Response
lcsh:Medicine
Disease Vectors
Biochemistry
Viral Packaging
law.invention
Mice
0302 clinical medicine
law
Immune Physiology
Medicine and Health Sciences
030212 general & internal medicine
Vector (molecular biology)
Malaria
Falciparum
Fluorescent Antibody Technique
Indirect
lcsh:Science
Immune Response
Immunity
Cellular
Mice
Inbred BALB C
Immune System Proteins
Multidisciplinary
Expression vector
biology
Recombinant Proteins
Infectious Diseases
Capsid
Recombinant DNA
Female
Viral Vectors
Antibody
Research Article
Immunology
Genetic Vectors
Plasmodium falciparum
Enzyme-Linked Immunosorbent Assay
Microbiology
Antibodies
Viral vector
03 medical and health sciences
Immune system
Antigen
Virology
Malaria Vaccines
Animals
Antigens
Adenoviruses
Human
lcsh:R
Immunity
Biology and Life Sciences
Proteins
Viral Replication
Species Interactions
Microscopy
Electron
030104 developmental biology
Humoral Immunity
biology.protein
Capsid Proteins
lcsh:Q
Viral Transmission and Infection
Zdroj: PLoS ONE, Vol 12, Iss 3, p e0174728 (2017)
PLoS ONE
ISSN: 1932-6203
Popis: Durable protection against complex pathogens is likely to require immunity that comprises both humoral and cellular responses. While heterologous prime-boost regimens based on recombinant, replication-incompetent Adenoviral vectors (AdV) and adjuvanted protein have been able to induce high levels of concomitant humoral and cellular responses, complex manufacturing and handling in the field may limit their success. To combine the benefits of genetic and protein-based vaccination within one vaccine construct and to facilitate their use, we generated Human Adenovirus 35 (HAdV35) vectors genetically encoding a model antigen based on the Plasmodium falciparum (P. falciparum) circumsporozoite (CS) protein and displaying a truncated version of the same antigen (CSshort) via protein IX on the capsid, with or without a flexible glycine-linker and/or a 45Å-spacer. The four tested pIX-antigen display variants were efficiently incorporated and presented on the HAdV35 capsid irrespective of whether a transgene was encoded or not. Transgene-expression and producibility of the display-/expression vectors were not impeded by the pIX-display. In mice, the pIX-modified vectors induced strong humoral antigen-specific immunity that increased with the inclusion of the linker-/spacer molecules, exceeded the responses induced by the genetic, transgene-expressing HAdV35 vector, and surpassed recombinant protein in potency. In addition, the pIX- display/expression vectors elicited high antigen-specific cellular immune responses that matched those of the genetic HAdV35 vector expressing CS. pIX-modified display-/expression HAdV vectors may therefore be a valuable technology for the development of vaccines against complex pathogens, especially in resource-limited settings.
Databáze: OpenAIRE
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