TY - JOUR
T1 - Comparison of the immune responses induced by soluble and particulate Plasmodium vivax circumsporozoite vaccine candidates formulated in AS01 in rhesus macaques
AU - Vanloubbeeck, Yannick
AU - Pichyangkul, Sathit
AU - Bayat, Babak
AU - Yongvanitchit, Kosol
AU - Bennett, Jason W.
AU - Sattabongkot, Jetsumon
AU - Schaecher, Kurt
AU - Ockenhouse, Christian F.
AU - Cohen, Joe
AU - Yadava, Anjali
AU - Donner, Marie Noëlle
AU - Garzé, Virginie
AU - Ska, Michael
AU - Ajhir, Nora
AU - Marchand, Martine
AU - Ware, Lisa A.
AU - Hall, Cysha
N1 - Funding Information:
The authors thank Mark Polhemus, Olivier Godeaux, Ripley Ballou, Pascal Mettens, Falgunee Parekh and Ashley Birkett for their help during the design and execution phases of the study; the members of the Department of Veterinary Medicine, AFRIMS, for their help in the execution of the study, and members of the Entomology Department, AFRIMS, for their support in providing P. vivax sporozoites. The development of VMP001 was supported by the United States Army Medical Materiel Development Activity and the Military Infectious Diseases Research Program, Fort Detrick, Maryland. Financial support for the NHP study was provided by MVI. The authors also thank Aram Afsar for technical help, Utaiwan Srichairatanakul and Amporn Chluaydumrong for processing the blood samples and helping with the cellular assays, Benedicte Van der Heyden, Marielle Collée and Chiara Graceffa for their help in the production and characterization of the CSV-S,S particles, Gaël de Lannoy and Marie-Pierre Malice for statistical analyses, Johan Vekemans and Ripley Ballou for their critical review of the manuscript. The authors also thank Ellen Oe, Ulrike Krause and Pascal Cadot for editorial assistance.
Funding Information:
This work was supported by GlaxoSmithKline Biologicals SA , the Walter Reed Army Institute of Research (WRAIR) and the PATH-Malaria Vaccine Initiative (MVI) . MVI was the funding source for the monkey study. GlaxoSmithKline Biologicals SA and WRAIR were involved in all stages of the study design, conduct and analysis. GlaxoSmithKline Biologicals SA also took in charge all costs associated with the development and the publishing of the present manuscript. All authors had full access to the data and had final responsibility to submit for publication.
PY - 2013/12/16
Y1 - 2013/12/16
N2 - We have designed a pre-erythrocytic vaccine candidate based on the Plasmodium vivax circumsporozoite (CSV) protein, which includes its N- and C-terminal parts and a truncated region containing repeat sequences from both the VK210 and the VK247 P. vivax subtypes. Two versions of this vaccine candidate were made: a soluble recombinant protein expressed in Escherichia coli, designated VMP001 and a particulate antigen expressed in Saccharomyces cerevisiae, designated CSV-S,S. The latter is composed of CSV-S, a fusion protein between VMP001 and hepatitis B surface antigen (HBsAg), and free HBsAg co-expressed in yeast and self-assembling into mixed particles. Both antigen versions, adjuvanted with AS01, were shown to be immunogenic in rhesus monkeys. CSV-S,S/AS01 induced higher levels of VMP001-specific antibodies than did VMP001/AS01. Antibody responses against the N- and C-terminal regions of CSV and the VK210 repeat motif were of a similar magnitude following immunization with either the soluble or the particulate antigen. However, antibodies against the AGDR region, a potentially protective B cell epitope, were only detected after immunization with CSV-S,S. Analysis of the induced CD4+ T cells highlighted different cytokine profiles depending on the antigen form. These results warrant further clinical evaluation of these two vaccine candidates to assess the added value of a particulate versus soluble form of CSV, in terms of both immunogenicity and protective efficacy.
AB - We have designed a pre-erythrocytic vaccine candidate based on the Plasmodium vivax circumsporozoite (CSV) protein, which includes its N- and C-terminal parts and a truncated region containing repeat sequences from both the VK210 and the VK247 P. vivax subtypes. Two versions of this vaccine candidate were made: a soluble recombinant protein expressed in Escherichia coli, designated VMP001 and a particulate antigen expressed in Saccharomyces cerevisiae, designated CSV-S,S. The latter is composed of CSV-S, a fusion protein between VMP001 and hepatitis B surface antigen (HBsAg), and free HBsAg co-expressed in yeast and self-assembling into mixed particles. Both antigen versions, adjuvanted with AS01, were shown to be immunogenic in rhesus monkeys. CSV-S,S/AS01 induced higher levels of VMP001-specific antibodies than did VMP001/AS01. Antibody responses against the N- and C-terminal regions of CSV and the VK210 repeat motif were of a similar magnitude following immunization with either the soluble or the particulate antigen. However, antibodies against the AGDR region, a potentially protective B cell epitope, were only detected after immunization with CSV-S,S. Analysis of the induced CD4+ T cells highlighted different cytokine profiles depending on the antigen form. These results warrant further clinical evaluation of these two vaccine candidates to assess the added value of a particulate versus soluble form of CSV, in terms of both immunogenicity and protective efficacy.
KW - AS01
KW - CSV-S,S
KW - Immune response
KW - Malaria
KW - Plasmodium vivax
KW - VMP001
UR - http://www.scopus.com/inward/record.url?scp=84888427814&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2013.10.041
DO - 10.1016/j.vaccine.2013.10.041
M3 - Article
C2 - 24144477
AN - SCOPUS:84888427814
SN - 0264-410X
VL - 31
SP - 6216
EP - 6224
JO - Vaccine
JF - Vaccine
IS - 52
ER -