Antibody and clinical responses in volunteers to immunization with malaria peptide–diphtheria toxoid conjugates

Abstract

SUMMARYTwenty residue peptides from the I85-200-kD and 45-kD merozoite surface antigens of the malaria parasite Plasmodium faleiparum were covalently linked to diphtheria toxoid as a carrier and used to immunize human volunteers with aluminium hydroxide as an adjuvant. Significant antibody levels were elicited by two boosting injections. The antibodies reacted with acetone methanol fixed merozoite membranes in an immunofluorescence assay, but no inhibition of merozoite reinvasion could be detected in in vitro cultures containing the antibodies. Antibody levels against the immunizing peptides declined markedly within 77 days after the third injection. No hypersensitivity was observed against the peptides. However, the volunteers developed hypersensitivity against diphtheria toxoid, and in particular a pronounced type IM (Arthus) hypersensitivity after three injections with the toxoid. This effect might appear to limit the use of peptide-diphtheria toxoid conjugates for human immunization. Several biochemical, haematological and immunological tests done on the volunteers showed no other adverse effects from the immunizations.

Immunogenicity of a malaria parasite antigen displayed by Lactococcus lactis in oral immunisations

“…Therefore, the find-ings suggest that foreign proteins expressed in L. lactis can also be used in oral vaccination procedures to elicit protective secretory antibodies in the gut. Antibody titres achieved by using both L. lactis display formats of MSA2 are better than those achieved by immunisation with plasmid DNA [34] or peptide-diphtheria toxoid conjugates [35] through the intramuscular and intradermal routes. Intramuscular immunisation with synthetic peptide polymers based on MSA2 B-cell epitopes elicited high-titre antibodies against the immunising peptide, which reacted only poorly with near-native MSA2 on merozoites [36].…”

Analysis of Historical Trends and Recent Elimination of Malaria from Sri Lanka and Its Applicability for Malaria Control in Other Countries

“…Recent fundamental scientific discoveries made in Sri Lanka that encouraged local malaria control efforts include: (a) formation of natural transmission-enhancing antibodies in vivax malaria ( 32 ), (b) greater malaria transmission as a result of vector population changes in the Mahaweli irrigation scheme ( 6 , 33 ), (c) presence of An. culicifacies sibling species in the country with differential vector potential ( 34 ), (d) identification of salinity-tolerant and potent malaria vector Anopheles sundaicus in coastal areas ( 35 ), and (e) one of the first clinical trials of a malaria vaccine ( 36 ). Simple educational booklets on malaria written in English and the two vernacular languages of Sinhalese and Tamil were produced by academics and physicians to promote the public understanding of malaria and its control ( 11 ).…”

Exosomes from Bone Marrow Dendritic Cells Pulsed with Diphtheria Toxoid Preferentially Induce Type 1 Antigen-Specific IgG Responses in Naive Recipients in the Absence of Free Antigen

“…DT, a highly immunogenic protein widely used as a carrier in conjugate vaccines, was selected as our model protein (17,18). BMDC were cultured in the presence or in the absence of DT for 48 h, and the exosomes were then purified from the culture supernatant.…”