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G H Campbell

Publications and source records attributed to G H Campbell.

At least 19 recordsLinked to original sources
PubMed1993

Immunogenicity of the Plasmodium falciparum asexual blood-stage synthetic peptide vaccine SPf66.

The immunogenicity of the cocktail vaccine SPf66 against Plasmodium falciparum was investigated in rabbits, monkeys, and human volunteers. This polymerized peptide vaccine incorporates a portion of each of the 35-kD, 55-kD, and 83-kD blood-stage proteins, linked by an amino acid sequence reproducing one repeat from the circumsporozoite protein of P. falciparum. Results from this study show that vaccination with this vaccine molecule elicited high titers of antibodies to SPf66 and its constituents, but these antibodies did not correlate with regular or sensitive indirect fluorescent antibody (IFA) titers to blood-stage malaria parasites. However, rabbits injected with individual peptides produced antibodies with low affinity to indefinite parasite structures by immunoelectron microscopy, and rabbits injected with SPf66 had high antibody titers against the peptide (NANP)40. Consequently, these anti-SPf66 serum samples recognized P. falciparum sporozoites in the IFA. Such reactivity was not observed in monkeys or human volunteers vaccinated with SPf66. In addition, SPf66 components were recognized by antibodies induced by natural infection in humans and by laboratory-monitored infections in Aotus monkeys. These results suggest that this vaccine candidate merits further developmental work to better define immune response elicited by the copolymer to the parasite.

Adolescent↗
PubMed1992

Inhibitory activity against sporozoites induced by antibodies directed against nonrepetitive regions of the circumsporozoite protein of Plasmodium vivax.

In previous studies, Saimiri sciureus boliviensis monkeys have been immunized with four recombinant proteins reproducing part of the circumsporozoite (CS) protein of Plasmodium vivax sporozoites (NS1(81) V20, rPvCS-1, rPvCS-2, rPv-CS-3), or with irradiated sporozoites of P. vivax Salvador I strain. To analyze the antibody response elicited against epitopes located outside the immunodominant repeat region of the CS protein, serum samples from these animals were tested for their ability to inhibit the in vitro development of liver stages of P. vivax VK247 strain, characterized from the other strains only by a specific repeat region on the CS protein. Results indicated that there is at least one protective B-cell epitope outside the repeat region of the CS protein of P. vivax sporozoites, and that this epitope can be expressed by irradiated sporozoites, rPvCS-1 and -3, but not by rPvCS-1 or NS1(81)V20. Therefore, we designed peptides from the amino acid sequences present both in rPvCS-2 and -3, but not included in the recombinant proteins rPvCS-1 and NS1(81)V20. Anti-peptide antibodies had no activity on the development of sporozoites of P. vivax Salvador I strain, into schizonts in primary culture of Saimiri monkey hepatocytes. In addition, antisporozoite antibodies did not react with any of the peptides. These results suggest that the in vitro inhibition observed in this study could depend upon the conformation of the CS protein. This study also demonstrates that antibody response to unnatural linear epitopes can be induced by immunization with recombinant proteins.

Amino Acid Sequence↗
PubMed1992

Malaria transmission and vector biology on Sainte Marie Island, Madagascar.

A 17-mo longitudinal malaria survey (November 1988-March 1990) was carried out on Sainte Marie Island, an area on the east coast of Madagascar which is frequently visited by tourists. During 706 man-nights of capture, 46,401 mosquitoes belonging to 32 species were caught. Sporozoite rates were determined by ELISA and incriminated Anopheles gambiae Giles s.s., An. funestus Giles, and An. mascarensis De Meillon as vectors of malaria. An. gambiae, the main vector, was highly anthropophilic but largely exophilic. Transmission by this species occurred mainly from November to April; the overall circumsporozoite antigen positivity rate was 1.7%, with a maximum of 3.2% in March-April. The nightly peak of transmission occurred between midnight and 0400 hours. The annual inoculation rate was calculated to be 100 infective bites per human, of which 92 were of Plasmodium falciparum. An. funestus played a minor role in transmission. An. mascarensis, an anopheline endemic to Madagascar, was incriminated for the first time, as a malaria vector. The sporozoite rate in this species varied from 0.4 to 0.9% as shown by both ELISA and salivary gland dissections. Parasite indices in humans up to 20 yr of age fluctuated during the year from 64 to 80%. Bed nets are recommended for malaria protection for the local population and tourists.

Animals↗
PubMed1992

Is Anopheles mascarensis a new malaria vector in Madagascar?

Anopheles mascarensis De Meillon, 1947, a mosquito that is native to Madagascar, is reported for the first time to act as a vector of Plasmodium falciparum malaria. From September 1989 to March 1990, 2, 499 An. mascarensis specimens from different regions of Madagascar were tested by an enzyme-linked immunosorbent assay (ELISA), using monoclonal antibodies against the circumsporozoite (CS) protein of the four human species of Plasmodium. The salivary glands of 237 specimens were also dissected. Fourteen of 1,864 specimens obtained from Sainte Marie island on the Malagasy east coast were found by ELISA to be positive for the CS protein of P. falciparum. In addition, two of 237 specimens that were dissected were observed to have sporozoites in the salivary glands. These sporozoites were identified as P. falciparum by ELISA. In the other regions studied, no positive specimens were found. Due to observed behavioral differences between east coast and highland populations of An. mascarensis, the possible presence of a species complex is discussed.

Animals↗
PubMed1992

Reinforcement of immunity in Saimiri monkeys following immunization with irradiated sporozoites of Plasmodium vivax.

To determine the duration of immunity to Plasmodium vivax following immunization, six Saimiri sciureus boliviensis monkeys were vaccinated with irradiated sporozoites of P. vivax and challenged multiple times with sporozoites. Over a period of almost four years, complete protection from repeated challenge with infective sporozoites was demonstrated in one monkey; protection in two monkeys was obtained on eight of nine occasions, in one monkey on seven of nine occasions, in one monkey on six or nine occasions, and in one monkey on four of eight occasions. Five of six monkeys were protected against infection during the last six challenges. Inoculation with blood-stage parasites at the end of the trial indicated that all animals were susceptible to infection. These results suggest that protection against sporozoite challenge may be strongly reinforced by subsequent exposure to viable sporozoites.

Animals↗
PubMed1992

Immunogenicity and efficacy trials in Aotus nancymai monkeys with model compounds representing parts of a 75-kD merozoite surface antigen of Plasmodium falciparum.

We tested the ability of a recombinant DNA-encoded fragment (C7Ag) of a Plasmodium falciparum merozoite protein (p75) and of two carrier-free peptide models (28-mer and 76-mer) to stimulate boostable antibody responses in Aotus nancymai monkeys. In addition, we evaluated protection against challenge with the Uganda Palo Alto (FUP) strain of this parasite. The data indicate that C7Ag elicited a strong and boostable IgG antibody response in all the monkeys immunized. However, studies with the peptide models demonstrated that various animals produce antibodies to different portions of this structure. When the post-boost sera from monkeys immunized with C7Ag were analyzed for reactivity against two major portions of C7Ag, most of the antibody response was observed against the disulfide-bonded 76-residue region that forms a conformational immunogenic epitope. In the same sera, antibody levels against the charged helical region modeled with a 28-mer were generally low. Immunization with synthetic peptides revealed that the 76-mer stimulated an antibody response almost as strong as C7Ag, with substantial cross-reactivity against the parasite antigen. The 28-mer evoked a response that was not efficient or uniform, and showed little reactivity with the authentic parasite antigen. Aotus nancymai was shown to be susceptible to infection with the Uganda Palo Alto strain of P. falciparum; however, maximum parasitemia varied markedly in both immunized and control monkeys. Statistical analysis failed to recognize differences in maximum parasitemia between the vaccine and control groups. The variation in maximum parasitemia suggests that the FUP strain in this species of Aotus is a poor model for the detection of differences in efficacy based on maximum parasitemia. This initial study with structures based on parts of the 75-kD merozoite surface antigen of P. falciparum indicated that both the recombinant-produced protein C7 and the 76-mer synthetic peptide, when combined with a Syntex adjuvant formulation, were safe and immunogenic in A. nancymai monkeys. However, the data emphasize the problems of using animal models to evaluate the potential effects of immunogens in humans.

Adjuvants, Immunologic↗
PubMed1991

Inability of malaria vaccine to induce antibodies to a protective epitope within its sequence.

Saimiri monkeys immunized with a recombinant protein containing 20 copies of the nine amino acid repeat of the Plasmodium vivax circumsporozoite (CS) protein developed high concentrations of antibodies to the repeat sequence and to sporozoites, but were not protected against challenge. After intravenous injection of an immunoglobulin G3 monoclonal antibody (NVS3) against irradiated P. vivax sporozoites, four of six monkeys were protected against sporozoite-induced malaria, and the remaining two animals took significantly longer to become parasitemic. Epitope mapping demonstrated that NVS3 recognizes only four (AGDR) of the nine amino acids within the repeat region of the P. vivax CS protein. The monkeys immunized with (DRAADGQPAG)20 did not produce antibodies to the protective epitope AGDR. Thus, determination of the fine specificity of protective immune responses may be critical to the construction of successful subunit vaccines.

Amino Acid Sequence↗
PubMed1991

Plasmodium cynomolgi: immunization of a rhesus monkey with exoerythrocytic stages cultured in autologous hepatocytes.

To investigate the immune response to exoerythrocytic stages of malaria parasites, a rhesus monkey was immunized with autologous primary hepatocyte cultures infected with 7-day-old liver stage parasites of Plasmodium cynomolgi. A primary antibody response against EE stage antigens was obtained, and boosted after injection of homologous viable sporozoites. Antibodies directed against sporozoites and blood stages were also detected. The polyvalent immune response observed demonstrates the antigenicity of the liver stages and suggests their involvement in the general immune response against malaria.

Animals↗
PubMed1991

Immunization of owl monkeys with the ring-infected erythrocyte surface antigen of Plasmodium falciparum.

Aotus nancymai were immunized with the 4-mer, 8-mer, and 11-mer repeat peptides of the ring-infected erythrocyte surface antigen molecule of Plasmodium falciparum conjugated to diphtheria toxoid with muramyl dipeptide (MDP) as adjuvant. Immunization failed to induce protective immunity against the Uganda Palo Alto strain of P. falciparum as judged by maximum levels of parasitemia of immunized monkeys relative to those of controls. The fused polypeptide FPAg632, when combined with MDP, also failed to induce protective immunity. However, the maximum level of parasitemia and serologic response to the 11-mer peptide were inversely correlated. The safety of the use of MDP was evident.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Significance of circumsporozoite-specific antibody in the natural transmission of Plasmodium falciparum, Plasmodium vivax, and Plasmodium malariae in an aboriginal (Orang Asli) population of central peninsula Malaysia.

Two hundred and seventy-five Orang Asli volunteers living in nine villages in the Pos Legap Valley of Perak State, peninsular Malaysia, participated in a prospective study designed to characterize the epidemiological, parasitological, and entomological characteristics of Plasmodium falciparum, P. vivax, and P. malariae malaria transmission. Prevalence rates for the three plasmodial species at initiation of the study ranged from 56% in the 0-4-year-old age group to 0% in individuals over the age of 40. Entomological surveys were conducted, enabling us to determine mosquito salivary gland-positive rates and entomological inoculation rates of 1.2 infectious mosquito bites per person per month for P. falciparum, 2.4 for P. vivax, and 0.3 for P. malariae. Cumulative incidence rates over the 16 weeks of the study, following radical cure of all volunteers, were 22.5% for P. falciparum, 12.7% for P. vivax, and 1.5% for P. malariae. The median baseline antibody titer against the immunodominant repetitive B cell epitope of P. falciparum or P. vivax circumsporozoite protein was significantly higher for volunteers who did not become parasitemic. Volunteers were selected for further study if they had evidence of being challenged with P. falciparum sporozoites during the study, based on a two-fold or greater increase in antibody titer against the immunodominant repetitive B cell epitope of the circumsporozoite protein. Resistance to infection was seen in six of 10 individuals who had high (greater than 25 OD units) baseline ELISA titers, compared with only three of 24 individuals who had low baseline ELISA titers (chi 2 P less than 0.02). A similar analysis for P. vivax did not show a significant correlation.

Adolescent↗
PubMed1991

[Longitudinal study on malaria transmission and biology of vectors in the island of Sainte Marie, on the east coast of Madagascar, from 1988 to 1990].

A 17-month longitudinal malaria survey was carried out in Sainte Marie Island, on the East Coast of Madagascar, from November 1988 to March 1990. During 706 man-nights of captures, 46401 mosquitoes belonging to 32 species were caught. Sporozoïte rates were calculated by Elisa. The malaria vectors were Anopheles gambiae sensu stricto, An. funestus and An. mascarensis. An. gambiae was the main vector. It was highly anthropophilic and partially exophilic. Transmission by this species mainly occurred from November to April, monthly sporozoïte antigene positivity rate varied from 0 to 3.85. The annual inoculation rate was about 100 infecting bites per man, in which 92 by Plasmodium falciparum. An. funestus intervened weakly in transmission. An. mascarensis, a malagasy endemic region anopheline is a newly discovered vector. The observed sporozoïte rate varied from 0.4 to 0.9 between September and March 1990. Parasite indexes in human fluctuated during the year from 64 to 80%. Because of the high level of transmission, recommendations for inhabitants and tourists are proposed.

Adolescent↗
PubMed1990

Malaria transmission and vector biology in Manarintsoa, high plateaux of Madagascar.

To evaluate the factors which determine the transmission level of falciparum malaria, entomological and parasitological surveys were conducted from October 1988 to February 1990 in Manarintsoa in the central highland plateaux of Madagascar. Mosquitoes were collected for 928 man-nights in pit shelters and indoor resting sites. Malaria vectors were Anopheles arabiensis and An. funestus, with no evidence of the presence of An. gambiae sensu stricto. Vectors were mainly exophilic and zoophilic. The index of stability was less than 1.5. The sporozoite rate was 0.11 for An. gambiae sensu lato and 0.47 for An. funestus. The transmission level was low, with an inoculation rate of 0.91 infective bites/person/year and an infection risk of 0.62. Malaria transmission occurs 7 months of the year in this area, from November to May. Human parasite rates fluctuated from 29% in October to 53% in May.

Animals↗
PubMed1990

Immunization of owl monkeys with a combination of Plasmodium falciparum asexual blood-stage synthetic peptide antigens.

A mixture of 3 synthetic peptides (35.1, 55.1, and 83.1) corresponding to portions of the 35 kDa, 55 kDa, and 83 kDa proteins from the asexual blood stages of Plasmodium falciparum and a polymer of a syntheic peptide incorporating the 3 individual peptides (SPf66) were tested as candidate malaria vaccine antigens in Aotus nancymai. Monkeys were immunized with combinations of the 3 peptides from 2 separate sources (Centers for Disease Control [CDC], Atlanta, GA or Colombia) or with the synthetic polymer. Animals immunized with a combination of the 3 peptides from CDC had higher antibody titers to the 35.1 and 55.1 peptides than to the 83.1 peptide. Monkeys immunized with a combination of the 3 peptides produced in Colombia developed higher levels of antibody to the 55.1 than to the 83.1 and 35.1 peptides. Animals immunized with the polymer produced detectable antibodies to the 55.1 peptide alone. Following challenge with P. falciparum, no differences were observed between the 3 vaccine groups and 2 control groups with respect to the number of animals with parasitemias greater than or equal to 10%. The inconsistency of serologic response to all 3 peptides in these animals contrasted with previous trials performed in Colombia where the monkeys developed high antibody titers against the 3 peptides and were protected against the experimental infection.

Amino Acid Sequence↗
PubMed1990

Further studies on the immunization of Saimiri sciureus boliviensis with recombinant vaccines based on the circumsporozoite protein of Plasmodium vivax.

Reported are the results of a trial in squirrel monkeys of 2 Plasmodium vivax malaria vaccine candidates based on the circumsporozoite (CS) protein, namely, rPvCs-2 and rPvCS-3. Compared with an earlier recombinant P. vivax CS construct, rPvCS-1, rPvCS-2 has an additional 24 amino acids at the C-terminal, which includes the thrombospondin region of homology and a putative T cell epitope. The rPvCS-3 was generated from a chemically synthesized gene that contained an additional 54 amino acids at the amino terminus and terminates at the same carboxy-terminal amino acid as rPvCS-2. In addition, rPvCS-3 contained only 1 each of the repeat sequences DRADGQPAG and DRAAGQPAG. Both antigens were administered with alum as adjuvant. Neither formulation caused toxic side effects and both recombinant molecules induced high antibody titers. Two monkeys were protected against sporozoite challenge by immunization with rPvCS-2 antigen, while none of the rPvCS-3 immunized animals displayed any degree of protection. While there was no correlation between protection and antibody titer or the in vitro proliferation of lymphocytes in response to the antigens, this is further evidence to support the role of the repeating epitopes in generating protective immunity.

Amino Acid Sequence↗
PubMed1990

[Malaria vectors and their role in transmission, in Manarintsoa in the Highland Plateaux of Madagascar from 1988 to 1990].

To evaluate the factors determining malaria transmission level, entomological and parasitological surveys were conducted from October 1988 to February 1990 in MANARINTSOA, in the central highland plateaux of MADAGASCAR. Mosquitoes were collected during 928 man-nights of captures, in pit shelters and in indoors resting sites. The malaria vectors were An. arabiensis and An. funestus, with no evidence of the presence of An. gambiae s.s. The vectors were mainly exophilic and zoophilic. The index of stability was below 1.5. The sporozoite rate was 0.11 for An. gambiae s.l. and 0.47 for An. funestus. The transmission level was low: the inoculation rate was 0.91 infected bite per man and per year and the infection risk 0.62. Transmission occurs 7 months per year, from November to May. In the human population parasite rates fluctuated from 29% in October to 53% in May.

Altitude↗
PubMed1989

Antibodies to Plasmodium falciparum ring-infected erythrocyte surface antigen and P. falciparum and P. malariae circumsporozoite proteins: seasonal prevalence in Kenyan villages.

Two cross-sectional surveys of 954 persons in Asembo Bay and Got Nyabondo, western Kenya, were performed in August-September 1986, after long rains, and in February-March 1987, after a comparatively dry season. Serologic testing was performed using an ELISA with synthetic peptides representing repeat amino acid sequences of the Plasmodium falciparum ring-infected erythrocyte surface antigen (RESA), (EENV)5, (EENVEHDA)4, and (DDEHVEEPTVA)2 and repeat sequences (PNAN)5 and (NAAG)5 of the P. falciparum and P. malariae circumsporozoite proteins. In 1986, 45%, 73%, 72%, 85%, and 59% of the persons in Asembo Bay had antibodies to the respective peptides. In Got Nyabondo, the rates were 44%, 67%, 56%, 36%, and 41%, respectively. All positivity rates increased with age. When next determined in 1987, the positivity rates and levels of reactivity were generally unchanged in Asembo Bay, but were decreased in Got Nyabondo.

Adolescent↗
PubMed1989

A nitrocellulose membrane-based ELISA for the detection of Plasmodium infections in mosquitos.

A nitrocellulose (NC) membrane was evaluated as a solid-phase support for the detection of malaria-infected mosquitos using monoclonal antibodies (MAb) with a laboratory model based on Plasmodium inui and Anopheles dirus. MAbs produced against sporozoites of the N34 strain of P. inui, and selected by immunofluorescence assay and the circumsporozoite precipitin test, were used. A one-site indirect NC-ELISA that used unlabelled MAb and enzyme-labelled anti-mouse IgG was developed. Its sensitivity was about 200 sporozoites and it reliably detected one infected mosquito in a pool of 20. This indirect NC-ELISA has the advantage that it does not require direct conjugation of the MAb to an enzyme or biotin. In the direct one-site NC-ELISA, which is also reported, the relatively simple biotinylation procedure was an alternative to the enzyme- or radiolabelled MAbs. The NC-ELISAs were simple and rapid. Furthermore, the indirect NC-ELISA can be used to detect sporozoite antigen localized in various body sectors of mosquitos.

Animals↗