Repeated infection of Aotus monkeys with Plasmodium falciparum induces protection against subsequent challenge with homologous and heterologous strains of parasite.

Abstract

Abstract. We evaluated repeated blood-stage infections with Plasmodium falciparum in eight Aotus lemurinus lemurinus monkeys. Over the course of seven infections with 10 4 P. falciparum (the Vietnam Oak Knoll [FVO] strain), the pre-patent period lengthened from 8.2 to 30.8 days; the peak parasitemia decreased from 4.5 ϫ 10 5 to 0 parasites/l (Challenges 6 and 7), and the requirement for treatment decreased from 100% to 0% (Challenges 3 to 7). Five weeks after the seventh FVO challenge, the eight immune and three naïve monkeys received 10 4 parasitized erythrocytes infected with P. falciparum (CAMP strain). The three control animals experienced uncontrolled parasitemias reaching between 4.8 and 7.7 ϫ 10 5 parasites/l (pre-patency ϭ 6.3 days) and all required drug treatment; six of the eight immune monkeys became parasitemic (pre-patency ϭ 8.8 days), but self-cured. Two of three of the monkeys having the greatest reductions in hematocrit (50-60%) also had the highest parasitemias (ϳ10 4 parasites/ l) before self-curing. Repeated homologous infections induced sterile immunity to homologous challenge; during heterologous challenge the monkeys developed clinically relevant, but not life-threatening, parasitemias and anemia.

Vaccination of Monkeys with RecombinantPlasmodium falciparumApical Membrane Antigen 1 Confers Protection against Blood-Stage Malaria

“…This is the first time we have observed a significant delay in patency as a result of vaccination. In eight published studies (and three unpublished studies by Stowers and coworkers) with A. nancymai or A. vociferans monkeys and MSP1-based vaccines (8,9,14,15,17,18), an MSP3 vaccine (10), or whole parasites (13), no significant delay in patency compared to that for control animals has been observed. The majority of these studies were performed with A. nancymai, so it is possible that a delay in patency is a characteristic of the A. vociferans model.…”

Anemia in parasite- and recombinant protein-immunized aotus monkeys infected with Plasmodium falciparum.

“…Three naïve control animals were included in the P. falciparum (CAMP strain) challenge. All challenges described in this study were performed by intravenous injection via the saphenous vein of 10 4 parasitized Aotus erythrocytes. 4 The 11 animals were assessed daily for 35 days for parasitemia, hematocrit levels were assessed on days 10, 14, 17, 21, 24, 28, 31, and 35.…”

“…Differences between the FVO and CAMP strains have been previously described. 4 Vaccine trial 1 with challenge and rechallenge. A total of 34 male and female Aotus nancymae monkeys were used in this study.…”

“…Modified DATs for IgG and complement component C3d were performed on days 1,4,8,13,16,20,24, and 28 of the 28-day follow-up period; all tests in all monkeys were negative.…”

Adaptation of a Thai Multidrug-Resistant C2A Clone of Plasmodium falciparum to Aotus Monkeys and Its Preliminary in vivo Antimalarial Drug Efficacy-Resistance Profile

“…lemurinus ) has been used to adapt new strains of malaria [7][8][9] study its biology, [10][11][12] pathogenesis of its infection, [13][14][15] and to test the efficacy and pharmacokinetics of antimalarial compounds [16][17][18][19][20][21][22][23][24][25][26][27] against these new strains. More recently, this model has also been used to test the efficacy and immunogenicity of antimalarial vaccines through the use of repeated challenge, 28 plasmid DNA vaccines, [29][30][31][32] temperature-sensitive mutants, 33 synthetic peptides, 34 recombinant proteins, [35][36][37] and even to test the immunogenicity of hepatitis B DNA vaccines. 38 Herein, we describe the adaptation of a new MDR C2A clone of P. falciparum originally from Thailand to Aotus l. lemurinus monkeys and present preliminary in vivo data on its drug sensitivity-resistance profile.…”