Comparison of the immune responses induced by soluble and particulate Plasmodium vivax circumsporozoite vaccine candidates formulated in AS01 in rhesus …

Y Vanloubbeeck, S Pichyangkul, B Bayat… - Vaccine, 2013 - Elsevier
Y Vanloubbeeck, S Pichyangkul, B Bayat, K Yongvanitchit, JW Bennett, J Sattabongkot…
Vaccine, 2013Elsevier
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 …
Abstract
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.
Elsevier