Blocking of Transmission to Mosquitoes by Antibody to Plasmodium Vivax Malaria Vaccine Candidates Pvs25 and Pvs28 Despite Antigenic Polymorphism in Field Isolates

Abstract

We have previously demonstrated that mouse antisera against yeast-produced recombinant forms of the ookinete surface proteins of Plasmodium vivax (Pvs25 and Pvs28) blocks transmission of the homologous P. vivax (Sal I strain). In this study, we developed mouse and rabbit antisera against Pvs25 and Pvs28 and evaluated the efficacy of these vaccine candidates against natural isolates of P. vivax in Thailand. Although both Pvs25 and Pvs28 genes are polymorphic, sera from mice immunized using alum adjuvant completely inhibited oocyst development for most human isolates, whereas sera from rabbits immunized with either alum or Freund's adjuvant were partially inhibitory. All inhibition occurred in an antibody dose dependent fashion. Data from this study clearly demonstrates that antibodies raised against Sal I-based vaccines overcome the genetic polymorphism of Pvs25 and Pvs28 present in natural isolates of P. vivax, suggesting the wide range applicability of Sal I based vaccines.

Human Host-Derived Cytokines Associated with Plasmodium vivax Transmission from Acute Malaria Patients to Anopheles darlingi Mosquitoes in the Peruvian Amazon

“…54 Currently, the development of transmission-blocking vaccines focuses on potential antibodies that interfere with transmission and several candidate antigens are being tested. [55][56][57][58] We also hypothesize that parasite reproductive behavior is guided by the parasite's nutritional milieu, i.e., the nutritional status of the host. 59 These many factors all play a role in the complex, dynamic process of transmission, and warrant further study in the pursuit of developing better tools with which to combat the burden of malaria on infected people and societies.…”

Transgenesis, Paratransgenesis and Transmission Blocking Vaccines to Prevent Insect-Borne Diseases

“…P. vivax ookinete development was completely blocked by the anti-serum against Pvs25 (Hisaeda et al 2000). Vaccination against Pvs25 and Pvs28 also presented efficient transmission blocking activity against P. vivax isolated from human patients, despite polymorphism in these proteins (Sattabongkot et al 2003).…”

“…In addition to identifying TBV candidates that are effective and may span different insect vector species, studies on TBV development must include antigenic variability present in field isolates (Kocken et al 1995;Drakeley et al 1996;Duffy & Kaslow 1997;Sattabongkot et al 2003), immunogenicity of such antigens (Kubler-Kielb et al 2007), reactogenicity caused by adjuvants (Saul et al 2007;Wu et al 2008), non-specific responses (Quakyi et al 1987;Tonui et al 2001a), and improper folding of antigens (Kaslow et al 1994;Milek et al 1998a;Milek et al 1998b;Milek et al 2000). Natural antigenic boosting is another important issue that must be dealt with (Arevalo-Herrera et al 2005).…”

“…P. falciparum proteins Pfs25, Pfs28, Pfs48/45, and Pfs230, and their orthologs in Plasmodium vivax, have been tested in transmission-blocking assays (Quakyi et al 1987;Kaslow et al 1988;Duffy & Kaslow 1997;Hisaeda et al 2000;Sattabongkot et al 2003;Malkin et al 2005;Outchkourov et al 2008). …”

“…Additionally, the antigen/adjuvant combination has to be safe enough to the vertebrate host so as to avoid side effects after immunization (Saul et al 2007;Wu et al 2008). Ideally, a TBV candidate antigen will display low levels of polymorphisms (in field isolates) so that a unique antigen may be used to produce a TBV capable of recognizing all the field variants of that specific antigen (Kocken et al 1995;Drakeley et al 1996;Duffy & Kaslow 1997;Sattabongkot et al 2003). Alternatively, an effective TBV may need to combine different antigens because the combined action of the antibodies against such antigens may produce a more efficient transmission-blocking result (Duffy & Kaslow 1997;Gozar et al 1998;Kongkasuriyachai et al 2004).…”