A Chimeric Plasmodium falciparum Merozoite Surface Protein Vaccine Induces High Titers of Parasite Growth Inhibitory Antibodies

Abstract

The C-terminal 19-kDa domain of Plasmodium falciparum merozoite surface protein 1 (PfMSP1 19 ) is an established target of protective antibodies. However, clinical trials of PfMSP1 42 , a leading blood-stage vaccine candidate which contains the protective epitopes of PfMSP1 19 , revealed suboptimal immunogenicity and efficacy. Based on proof-of-concept studies in the Plasmodium yoelii murine model, we produced a chimeric vaccine antigen containing recombinant PfMSP1 19 (rPfMSP1 19 ) fused to the N terminus of P. falciparum merozoite surface protein 8 that lacked its low-complexity Asn/Asp-rich domain, rPfMSP8 (⌬Asn/ Asp). Immunization of mice with the chimeric rPfMSP1/8 vaccine elicited strong T cell responses to conserved epitopes associated with the rPfMSP8 (⌬Asn/Asp) fusion partner. While specific for PfMSP8, this T cell response was adequate to provide help for the production of high titers of antibodies to both PfMSP1 19 and rPfMSP8 (⌬Asn/Asp) components. This occurred with formulations adjuvanted with either Quil A or with Montanide ISA 720 plus CpG oligodeoxynucleotide (ODN) and was observed in both inbred and outbred strains of mice. PfMSP1/8-induced antibodies were highly reactive with two major alleles of PfMSP1 19 (FVO and 3D7). Of particular interest, immunization with PfMSP1/8 elicited higher titers of PfMSP1 19 -specific antibodies than a combined formulation of rPfMSP1 42 and rPfMSP8 (⌬Asn/Asp). As a measure of functionality, PfMSP1/8-specific rabbit IgG was shown to potently inhibit the in vitro growth of blood-stage parasites of the FVO and 3D7 strains of P. falciparum. These data support the further testing and evaluation of this chimeric PfMSP1/8 antigen as a component of a multivalent vaccine for P. falciparum malaria.

Survey of bluetongue virus infection in free-ranging wild ruminants in Switzerland

“…In contrast, two virus positive animals (one chamois and one roe deer) originated from regions where no domestic BT outbreak has been reported so far [16], at a distance of 38.0 km and 85.5 km, respectively, to the next community with a documented outbreak.…”

“…First, albeit 76 BT outbreaks have been recorded in Swiss livestock between 2007 and 2010 [16], this number is very low compared to the situation observed in other countries [26], e.g. 26,500 herds with clinical cases in 2008 in France [27].…”

“…This supports the hypothesis that, although they live in the same habitat, red deer are more susceptible to infection than roe deer. It is interesting to note that red deer are abundant in the southern part of the Swiss Jura while only few individuals are present in its northern part [29], where most of the domestic Swiss BT outbreaks occurred [16]. In contrast, roe deer and chamois are abundant in the northern Jura [29] but none of the individuals from this region (133 samples) were positive.…”

“…The first BTV-8 infection in a domestic animal in Switzerland was diagnosed at the end of October 2007 [13] and in 2008, like in most European countries confronted to the BT epidemic, a large scale compulsory vaccination campaign was initiated to limit the expansion of the virus [15]. From 2007 to 2010, 76 local outbreaks have been reported in Swiss livestock [16]. A study in wildlife prior to the 2007 epidemic reported no evidence of BTV infection in Swiss red deer [17].…”

Vaccines to combat river blindness: expression, selection and formulation of vaccines against infection with Onchocerca volvulus in a mouse model

“…Even in the face of the significantly enhanced antibody titers the levels of protective immunity were not enhanced in the mice immunized with the double or triple fusion proteins. Fusion protein vaccines developed against Plasmodium falciparum have better efficacy than antigen cocktails (Faber et al, 2007, 2013; Alaro et al, 2013). A multivalent fusion protein vaccine against B. malayi conferred 95% protection in mice (Dakshinamoorthy et al, 2013).…”