Plasmodium falciparum:Heterologous Synthesis of the Transmission-Blocking Vaccine Candidate Pfs48/45 in Recombinant Vaccinia Virus-Infected Cells

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

“…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).…”

“…Another interesting aspect of TBVs is the possibility of natural boosting of the immune response of animals infected with a pathogen (i.e., pre-immunized) (Milek et al 1998a;Arevalo-Herrera et al 2005). Hence, candidate TBV proteins expressed on the surface of both insect-stage and blood-stage pathogens may induce activation of the immune response in infected hosts vaccinated with the same antigens (Arevalo-Herrera et al 2005).…”

“…Hence, candidate TBV proteins expressed on the surface of both insect-stage and blood-stage pathogens may induce activation of the immune response in infected hosts vaccinated with the same antigens (Arevalo-Herrera et al 2005). However, this approach may not be suitable to every TBV, such as Pvs25 which displays low expression in blood-stage P. vivax (Arevalo-Herrera et al 2005), and has yet to be demonstrated for the Plasmodium TBV-antigen candidates that are expressed during gametocytogenesis, for example, Pfs230 (Quakyi et al 1987) and Pfs48/45 (Milek et al 1998a). Proper folding of the TBV candidate protein following expression via recombinant techniques also may affect the efficacy of the vaccinating antigen.…”

Transmission blocking vaccines to control insect-borne diseases: a review

“…This protein is expressed on P. falciparum gametocyte and gamete surfaces and has a central role in male gamete fertility (van Dijk et al 2001). Attempts to express this protein in its native form using different systems, such as bacteria (Milek et al 1998a), Vaccinia virus (Milek et al 1998b) and yeast (Milek et al 2000) have failed due to improper folding. However, expression of a truncated form of Pfs48/45 (Pfs48/45-10C) in E. coli followed by steps of chemical-induced refolding produced 10-20% of correctly folded Pfs48/45-10C (Outchkourov et al 2007).…”

“…Challenges and perspectives on TBVs -In addition to identifying TBV candidates that are effective and may span different insect vector species, challenges to TBV development also encompass 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, b, 2000. Natural antigenic boosting is another important issue that must be dealt with (Arevalo-Herrera et al 2005).…”