I. The Characteristics of Untreated Sporozoite-Induced and Trophozoite-Induced Infections

Schmidt, Thomas; Fradkin, Rochelle; Genther, Clara S.; Rossan, Richard N.; Squires, Wanda

doi:10.4269/ajtmh.1982.31.612

Cited by 33 publications

(42 citation statements)

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“…(T1BT*) 4X immune serum giving 95% inhibition and STF2⌬.CS immune serum giving 99% inhibition. Inhibition of Ͼ90% is considered significant, as a 90% reduction in sporozoite numbers is required to give a 1-day delay in the prepatent period following sporozoite challenge (39)(40)(41).…”

Section: Resultsmentioning

confidence: 99%

“…The number of 18S rRNA copies in each sample was based on a standard curve generated with known amounts of plasmid 18S cDNA. Inhibition of Ͼ90% of 18S rRNA copy numbers compared to that in naive challenged mice was considered significant, based on previous studies using intravenous injection of known numbers of sporozoites which demonstrated that a log reduction in sporozoite numbers is required to give a 1-day delay in the prepatent period (1,(39)(40)(41).…”

Section: Dendritic Cells (Dc) (I) Murine DCmentioning

confidence: 99%

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Protective Humoral Immunity Elicited by a Needle-Free Malaria Vaccine Comprised of a Chimeric Plasmodium falciparum Circumsporozoite Protein and a Toll-Like Receptor 5 Agonist, Flagellin

et al. 2013

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bImmunization with Plasmodium sporozoites can elicit high levels of sterile immunity, and neutralizing antibodies from protected hosts are known to target the repeat region of the circumsporozoite (CS) protein on the parasite surface. CS-based subunit vaccines have been hampered by suboptimal immunogenicity and the requirement for strong adjuvants to elicit effective humoral immunity. Pathogen-associated molecular patterns (PAMPs) that signal through Toll-like receptors (TLRs) can function as potent adjuvants for innate and adaptive immunity. We examined the immunogenicity of recombinant proteins containing a TLR5 agonist, flagellin, and either full-length or selected epitopes of the Plasmodium falciparum CS protein. Mice immunized with either of the flagellin-modified CS constructs, administered intranasally (i.n.) or subcutaneously (s.c.), developed similar levels of malaria-specific IgG1 antibody and interleukin-5 (IL-5)-producing T cells. Importantly, immunization via the i.n. but not the s.c. route elicited sporozoite neutralizing antibodies capable of inhibiting >90% of sporozoite invasion in vitro and in vivo, as measured using a transgenic rodent parasite expressing P. falciparum CS repeats. These findings demonstrate that functional sporozoite neutralizing antibody can be elicited by i.n. immunization with a flagellin-modified P. falciparum CS protein and raise the potential of a scalable, safe, needle-free vaccine for the 40% of the world's population at risk of malaria.

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Section: Resultsmentioning

confidence: 99%

Section: Dendritic Cells (Dc) (I) Murine DCmentioning

confidence: 99%

Protective Humoral Immunity Elicited by a Needle-Free Malaria Vaccine Comprised of a Chimeric Plasmodium falciparum Circumsporozoite Protein and a Toll-Like Receptor 5 Agonist, Flagellin

et al. 2013

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“…Questions were also raised by , who thought that the cyclic theory of relapse was more compatible with the number of relapses, the relapse interval, and the regularity of relapse he had documented in his extensive work with rhesus monkeys infected with P. cynomolgi (74). Close examination of Schmidt's voluminous data shows that the interval values were obtained by averaging observations from a large number of monkeys, and, in fact, the ranges of intervals for the duration of relapse were fairly long.…”

Section: Theories Of Relapsementioning

confidence: 99%

The hypnozoite and relapse in primate malaria

1992

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Although the phenomenon of malarial relapse was known to the ancients, the mechanism has only recently been explained satisfactorily. The long-held hypothesis of a tissue "cycle" in primate malaria as a cause of relapse did not fit clinical and experimental observations. A latent stage for Plasmodium spp. in the liver, for which there is now extensive morphological and experimental confirmation, best explains both the relapse phenomenon and the long prepatent periods seen with some strains of Plasmodium vivax. These latent stages (hypnozoites) have been detected in three relapsing malarias and have been found to persist in the liver as uninucleate parasites for up to 229 days after sporozoite inoculation. They have been found in in vitro cultures of two species of Plasmodium, and their ultrastructure has been partially described.

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“…At the time of assignment to an experiment, 94 of the 306 monkeys weighed between 2.3 and 2.9 kg, 147 weighed between 3.0 and 3.9 kg, 56 weighed between 4.0 and 4.9 kg, and 9 weighed between 5.2 and 7.4 kg. The procedures for acquiring these monkeys, transporting them from New Delhi to Davis, Calif., and conditioning them for experimental use, routine colony husbandry practices (including dietary management), and methods of handling for all facets of the studies without resort to sedatives, tranquilizers, anesthetics, or squeeze cages were identical with those described previously (33,35,37).…”

Section: Rc-12 [12-dimethoxy-4-(bis-diethylaminoethyl)-amino-5-mentioning

confidence: 99%

“…The latter strain served a single assessment of prophylactic activity, and the B strain served all other assessments of prophylactic activity and all assessments of radical curative and suppressive activities. The origins of these strains, their maintenance via serial monkey-to-mosquito-to-monkey passages, the characteristics of untreated sporozoite-induced and trophozoite-induced infections, and the responses of such infections to standard blood and tissue schizonticidal drugs have been detailed previously (35,36,39). The evaluations of prophylactic and radical curative activities were carried out on monkeys inoculated intravenously with 7.9 x 104 to 1.2 x 106 sporozoites derived from the ground thoraces of Anopheles freeborni with heavily infected salivary glands.…”

Section: Rc-12 [12-dimethoxy-4-(bis-diethylaminoethyl)-amino-5-mentioning

confidence: 99%

Antimalarial activities and subacute toxicity of RC-12, a 4-amino-substituted pyrocatechol

Schmidt¹,

Rossan²,

Fradkin³

et al. 1985

Antimicrob Agents Chemother

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RC-12 [1,2-dimethoxy-4-(bis-diethylaminoethyl)-amino-5-bromobenzeneI was evaluated for prophylactic, radical curative, and suppressive activities against infections with Plasmodium cynomolgi and subacute toxicity in rhesus monkeys. Applied as a prophylactic agent, RC-12, administered in doses of 6.25 to 25.0 mg/kg daily throughout the incubation period, provided near-complete to complete protection against 105 to 106 times the minimum infective dose of sporozoites. Applied as a suppressive agent, daily doses of 100.0 mg of RC-12 per kg did not eradicate blood schizonts regularly; hence, the need for concomitant administration of a blood schizonticide, such as chloroquine, in assessments of radical curative activity. In such appraisals, daily doses of 6.25 to 25.0 mg of RC-12 per kg for 14 days, in combination with 2.5 mg of chloroquine per kg daily for 7 days, effected cure of 69 and 93% of established infections, respectively. The curative activity of RC-12 was related to the total dose and could be achieved with a regimen as brief as 4 days. With respect to outward expressions of toxicity, daily doses of 50.0 mg/kg or lower for 15 to 225 days evoked no reactions. Doses of 100.0 or 200.0 mg/kg, scheduled for 15 days, evoked convulsions and depression and were, respectively, lethal to 4 of 17 and 7 of 7 recipients. Doses of 25.0 mg/kg or lower evoked no discrete reactions. Doses of 50.0 mg/kg and higher evoked hepatomegaly, vacuolation of hepatocytes, and elevations of glutamic oxalacetic and glutamic pyruvic transferase activities in serum, reactions related in intensity to dose but not duration of dosage.

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I. The Characteristics of Untreated Sporozoite-Induced and Trophozoite-Induced Infections

Cited by 33 publications

References 0 publications

Protective Humoral Immunity Elicited by a Needle-Free Malaria Vaccine Comprised of a Chimeric Plasmodium falciparum Circumsporozoite Protein and a Toll-Like Receptor 5 Agonist, Flagellin

Protective Humoral Immunity Elicited by a Needle-Free Malaria Vaccine Comprised of a Chimeric Plasmodium falciparum Circumsporozoite Protein and a Toll-Like Receptor 5 Agonist, Flagellin

The hypnozoite and relapse in primate malaria

Antimalarial activities and subacute toxicity of RC-12, a 4-amino-substituted pyrocatechol

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