A recombinant vaccine expressed in the milk of transgenic mice protects Aotus monkeys from a lethal challenge with Plasmodium falciparum

Abstract

Two strains of transgenic mice have been generated that secrete into their milk a malaria vaccine candidate, the 42-kDa C-terminal portion of Plasmodium falciparum merozoite surface protein 1 (MSP142). One strain secretes an MSP142 with an amino acid sequence homologous to that of the FVO parasite line, the other an MSP142 where two putative N-linked glycosylation sites in the FVO sequence have been removed. Both forms of MSP142 were purified from whole milk to greater than 91% homogeneity at high yields.

Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya

“…Second, antibodies raised in animals against MSP-1 42 or the 19 kDa fragment inhibit the growth of P. falciparum in vitro [12]. Third, immunization of New World monkeys with recombinant MSP-1 formulated with a potent adjuvant confers protection against blood stage challenge with P. falciparum [13][14][15].…”

Preparation of recombinant proteins in milk to improve human and animal health

“…This is due to the presence of very high amounts of milk proteins and to the fact that some recombinant proteins may be trapped within casein micelles or bound to milk lipids [40].…”

Plasmodium falciparum: Immunization with MSP1-42 induced non-inhibitory antibodies that have no blocking activities but enhanced the potency of inhibitory anti-MSP1-42 antibodies

“…We and others have focused on the development of P. falciparum MSP1-42 vaccines (Chang et al, 1996;Stowers et al, 2001;Stowers et al, 2002;Darko et al, 2005), and since immunization with MSP1-42 primarily induced anti-MSP1-19 antibodies Kaslow et al, 1994), this raises the concern that active vaccination may induce blocking antibodies. This scenario is more detrimental than a MSP1 vaccine that has no efficacy since the resulting immune response may interfere with subsequent vaccine attempts to induce protective anti-MSP1 immunity.…”

“…Vaccine design has focused on the Cterminal 42 kDa region of MSP1 (MSP1-42) and its 19 kDa sub-fragment, MSP1-19 (Kumar et al, 1995;Chang et al, 1996;Stowers et al, 2001;Stowers et al, 2002;Darko et al, 2005). Phase I clinical testings of prototype MSP1-42 and MSP1-19 vaccines are well underway (Keitel et al, 1999;Pichyangkul et al, 2004).…”