Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Carter Diggs is active.

Publication


Featured researches published by Carter Diggs.


PLOS ONE | 2009

Blood Stage Malaria Vaccine Eliciting High Antigen-Specific Antibody Concentrations Confers No Protection to Young Children in Western Kenya

Bernhards Ogutu; Odika J. Apollo; Denise McKinney; Willis Okoth; Joram Siangla; Filip Dubovsky; Kathryn Tucker; John N. Waitumbi; Carter Diggs; Janet Wittes; Elissa Malkin; Amanda Leach; Lorraine Soisson; Jessica Milman; Lucas Otieno; Carolyn A. Holland; Mark E. Polhemus; Shon Remich; Christian F. Ockenhouse; Joe Cohen; W. Ripley Ballou; Samuel K. Martin; Evelina Angov; V. Ann Stewart; Jeffrey A. Lyon; D. Gray Heppner; Mark R. Withers

Objective The antigen, falciparum malaria protein 1 (FMP1), represents the 42-kDa C-terminal fragment of merozoite surface protein-1 (MSP-1) of the 3D7 clone of P. falciparum. Formulated with AS02 (a proprietary Adjuvant System), it constitutes the FMP1/AS02 candidate malaria vaccine. We evaluated this vaccines safety, immunogenicity, and efficacy in African children. Methods A randomised, double-blind, Phase IIb, comparator-controlled trial.The trial was conducted in 13 field stations of one mile radii within Kombewa Division, Nyanza Province, Western Kenya, an area of holoendemic transmission of P. falciparum. We enrolled 400 children aged 12–47 months in general good health.Children were randomised in a 1∶1 fashion to receive either FMP1/AS02 (50 µg) or Rabipur® rabies vaccine. Vaccinations were administered on a 0, 1, and 2 month schedule. The primary study endpoint was time to first clinical episode of P. falciparum malaria (temperature ≥37.5°C with asexual parasitaemia of ≥50,000 parasites/µL of blood) occurring between 14 days and six months after a third dose. Case detection was both active and passive. Safety and immunogenicity were evaluated for eight months after first immunisations; vaccine efficacy (VE) was measured over a six-month period following third vaccinations. Results 374 of 400 children received all three doses and completed six months of follow-up. FMP1/AS02 had a good safety profile and was well-tolerated but more reactogenic than the comparator. Geometric mean anti-MSP-142 antibody concentrations increased from1.3 µg/mL to 27.3 µg/mL in the FMP1/AS02 recipients, but were unchanged in controls. 97 children in the FMP1/AS02 group and 98 controls had a primary endpoint episode. Overall VE was 5.1% (95% CI: −26% to +28%; p-value = 0.7). Conclusions FMP1/AS02 is not a promising candidate for further development as a monovalent malaria vaccine. Future MSP-142 vaccine development should focus on other formulations and antigen constructs. Trial Registration Clinicaltrials.gov NCT00223990


The New England Journal of Medicine | 2011

A Field Trial to Assess a Blood-Stage Malaria Vaccine

Mahamadou A. Thera; Ogobara K. Doumbo; Drissa Coulibaly; Matthew B. Laurens; Amed Ouattara; Abdoulaye K. Kone; Ando Guindo; Karim Traore; Idrissa Traore; Bourema Kouriba; Dapa A. Diallo; Issa Diarra; Modibo Daou; Amagana Dolo; Youssouf Tolo; Mahamadou S Sissoko; Amadou Niangaly; Mady Sissoko; Shannon Takala-Harrison; Kirsten E. Lyke; Yukun Wu; William C. Blackwelder; Olivier Godeaux; Johan Vekemans; Marie-Claude Dubois; W. Ripley Ballou; Joe Cohen; Darby Thompson; Tina Dube; Lorraine Soisson

BACKGROUND Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02(A), a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children. METHODS In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain. RESULTS The cumulative incidence of the primary end point was 48.4% in the malaria-vaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval [CI], 0.63 to 1.09; P=0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P=0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine. CONCLUSIONS On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00460525.).


The Journal of Infectious Diseases | 2000

Synthetic Malaria Peptide Vaccine Elicits High Levels of Antibodies in Vaccinees of Defined HLA Genotypes

Elizabeth Nardin; Giane A. Oliveira; J. Mauricio Calvo-Calle; Z.Rosa Moya Castro; Ruth S. Nussenzweig; Barbara Schmeckpeper; B. Fenton Hall; Carter Diggs; Sacared A Bodison; Robert Edelman

A multiple antigen peptide (MAP) malaria vaccine containing minimal Plasmodium falciparum circumsporozoite protein repeat epitopes was assessed for safety and immunogenicity in volunteers of known class II genotypes. The MAP/alum/QS-21 vaccine formulation elicited high levels of parasite-specific antibodies in 10 of 12 volunteers expressing DQB1*0603, DRB1*0401, or DRB1*1101 class II molecules. In contrast, volunteers of other HLA genotypes were low responders or nonresponders. A second study of 7 volunteers confirmed the correlation of class II genotype and high responder phenotype. This is the first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids (N, A, V, D, and P) can elicit antibody titers comparable to multiple exposures to irradiated P. falciparum-infected mosquitoes. Moreover, the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro, thus facilitating the rational design of epitope-based peptide vaccines for malaria, as well as for other pathogens.


PLOS ONE | 2009

Phase 1/2a Study of the Malaria Vaccine Candidate Apical Membrane Antigen-1 (AMA-1) Administered in Adjuvant System AS01B or AS02A

Michele Spring; James F. Cummings; Christian F. Ockenhouse; Sheetij Dutta; Randall Reidler; Evelina Angov; Elke S. Bergmann-Leitner; V. Ann Stewart; Stacey Bittner; Laure Y. Juompan; Mark G. Kortepeter; Robin Nielsen; Urszula Krzych; Ev Tierney; Lisa A. Ware; Megan Dowler; Cornelus C. Hermsen; Robert W. Sauerwein; Sake J. de Vlas; Opokua Ofori-Anyinam; David E. Lanar; Jack Williams; Kent E. Kester; Kathryn Tucker; Meng Shi; Elissa Malkin; Carole A. Long; Carter Diggs; Lorraine Soisson; Marie-Claude Dubois

Background This Phase 1/2a study evaluated the safety, immunogenicity, and efficacy of an experimental malaria vaccine comprised of the recombinant Plasmodium falciparum protein apical membrane antigen-1 (AMA-1) representing the 3D7 allele formulated with either the AS01B or AS02A Adjuvant Systems. Methodology/Principal Findings After a preliminary safety evaluation of low dose AMA-1/AS01B (10 µg/0.5 mL) in 5 adults, 30 malaria-naïve adults were randomly allocated to receive full dose (50 µg/0.5 mL) of AMA-1/AS01B (n = 15) or AMA-1/AS02A (n = 15), followed by a malaria challenge. All vaccinations were administered intramuscularly on a 0-, 1-, 2-month schedule. All volunteers experienced transient injection site erythema, swelling and pain. Two weeks post-third vaccination, anti-AMA-1 Geometric Mean Antibody Concentrations (GMCs) with 95% Confidence Intervals (CIs) were high: low dose AMA-1/AS01B 196 µg/mL (103–371 µg/mL), full dose AMA-1/AS01B 279 µg/mL (210–369 µg/mL) and full dose AMA-1/AS02A 216 µg/mL (169–276 µg/mL) with no significant difference among the 3 groups. The three vaccine formulations elicited equivalent functional antibody responses, as measured by growth inhibition assay (GIA), against homologous but not against heterologous (FVO) parasites as well as demonstrable interferon-gamma (IFN-γ) responses. To assess efficacy, volunteers were challenged with P. falciparum-infected mosquitoes, and all became parasitemic, with no significant difference in the prepatent period by either light microscopy or quantitative polymerase chain reaction (qPCR). However, a small but significant reduction of parasitemia in the AMA-1/AS02A group was seen with a statistical model employing qPCR measurements. Significance All three vaccine formulations were found to be safe and highly immunogenic. These immune responses did not translate into significant vaccine efficacy in malaria-naïve adults employing a primary sporozoite challenge model, but encouragingly, estimation of parasite growth rates from qPCR data may suggest a partial biological effect of the vaccine. Further evaluation of the immunogenicity and efficacy of the AMA-1/AS02A formulation is ongoing in a malaria-experienced pediatric population in Mali. Trial Registration www.clinicaltrials.gov NCT00385047


Infection and Immunity | 2000

Immunogenicity and Efficacy in Aotus Monkeys of Four Recombinant Plasmodium falciparum Vaccines in Multiple Adjuvant Formulations Based on the 19-Kilodalton C Terminus of Merozoite Surface Protein 1

Sanjai Kumar; William E. Collins; Andrea Egan; Anjali Yadava; Olivier Garraud; Michael J. Blackman; José A. Guevara Patiño; Carter Diggs; David C. Kaslow

ABSTRACT The immunogenicity and protective efficacy of four versions of recombinant C-terminal 19-kDa epidermal growth factor-like region of the major surface protein 1 (rMSP119) of Plasmodium falciparum was studied in Aotus monkeys. Vaccination with each of the four rMSP119 constructs elicited high levels of antibodies to MSP119 but only one construct, the 19-kDa fragment expressed as a secreted fusion protein fromSaccharomyces cerevisiae (yP30P2MSP119), induced a high degree of protective immunity in Aotus nancymai against lethal P. falciparum challenge. Protective formulation required Freunds adjuvant; vaccination with yP30P2MSP119 in six other adjuvants that are suitable for human use induced lower levels of antibody response and no protection. These results emphasize the need to continue the search for an adjuvant that is comparable to Freunds adjuvant in potency and is safe for use in humans.


PLOS ONE | 2013

DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity.

Ilin Chuang; Martha Sedegah; Susan Cicatelli; Michele Spring; Mark E. Polhemus; Cindy Tamminga; Noelle B. Patterson; Melanie L. Guerrero; Jason W. Bennett; Shannon McGrath; Harini Ganeshan; Maria Belmonte; Fouzia Farooq; Esteban Abot; Jo Glenna Banania; Jun Huang; Rhonda Newcomer; Lisa Rein; Dianne Litilit; Nancy O. Richie; Chloe Wood; Jittawadee Murphy; Robert W. Sauerwein; Cornelus C. Hermsen; Andrea McCoy; Edwin Kamau; James F. Cummings; Jack Komisar; Awalludin Sutamihardja; Meng Shi

Background Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection. Methodology/Principal Findings The vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea), possibly related to immunization, was severe (Grade 3), preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27%) were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44–817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5–102) and were not associated with protection. Ex vivo IFN-γ ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13–408; AMA1 348, range 88–1270) and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019). Flow cytometry identified predominant IFN-γ mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant. Significance The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%). Protection was associated with cell-mediated immunity to AMA1, with CSP probably contributing. Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection. Trial Registration ClinicalTrials.govNCT00870987.


PLOS ONE | 2008

Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.

Mahamadou A. Thera; Ogobara K. Doumbo; Drissa Coulibaly; Dapa A. Diallo; Abdoulaye K. Kone; Ando Guindo; Karim Traore; Alassane Dicko; Issaka Sagara; Mahamadou S Sissoko; Mounirou Baby; Mady Sissoko; Issa Diarra; Amadou Niangaly; Amagana Dolo; Modibo Daou; Sory I. Diawara; D. Gray Heppner; V. Ann Stewart; Evelina Angov; Elke S. Bergmann-Leitner; David E. Lanar; Sheetij Dutta; Lorraine Soisson; Carter Diggs; Amanda Leach; Alex Owusu; Marie-Claude Dubois; Joe Cohen; Jason N. Nixon

Background The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria. Methodology/Principal Findings A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18–55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 µg/AS02A 0.25 mL or FMP2.1 50 µg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively. Conclusion/Significance The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site. Trial Registration ClinicalTrials.gov NCT00308061


Infection and Immunity | 2005

The Clinical-Grade 42-Kilodalton Fragment of Merozoite Surface Protein 1 of Plasmodium falciparum Strain FVO Expressed in Escherichia coli Protects Aotus nancymai against Challenge with Homologous Erythrocytic-Stage Parasites

Christian A. Darko; Evelina Angov; William E. Collins; Elke S. Bergmann-Leitner; Autumn S. Girouard; Stacy L. Hitt; Jana S. McBride; Carter Diggs; Anthony A. Holder; Carole A. Long; John W. Barnwell; Jeffrey A. Lyon

ABSTRACT A 42-kDa fragment from the C terminus of major merozoite surface protein 1 (MSP1) is among the leading malaria vaccine candidates that target infection by asexual erythrocytic-stage malaria parasites. The MSP142 gene fragment from the Vietnam-Oak Knoll (FVO) strain of Plasmodium falciparum was expressed as a soluble protein in Escherichia coli and purified according to good manufacturing practices. This clinical-grade recombinant protein retained some important elements of correct structure, as it was reactive with several functional, conformation-dependent monoclonal antibodies raised against P. falciparum malaria parasites, it induced antibodies (Abs) that were reactive to parasites in immunofluorescent Ab tests, and it induced strong growth and invasion inhibitory antisera in New Zealand White rabbits. The antigen quality was further evaluated by vaccinating Aotus nancymai monkeys and challenging them with homologous P. falciparum FVO erythrocytic-stage malaria parasites. The trial included two control groups, one vaccinated with the sexual-stage-specific antigen of Plasmodium vivax, Pvs25, as a negative control, and the other vaccinated with baculovirus-expressed MSP142 (FVO) as a positive control. Enzyme-linked immunosorbent assay (ELISA) Ab titers induced by E. coli MSP142 were significantly higher than those induced by the baculovirus-expressed antigen. None of the six monkeys that were vaccinated with the E. coli MSP142 antigen required treatment for uncontrolled parasitemia, but two required treatment for anemia. Protective immunity in these monkeys correlated with the ELISA Ab titer against the p19 fragment and the epidermal growth factor (EGF)-like domain 2 fragment of MSP142, but not the MSP142 protein itself or the EGF-like domain 1 fragment. Soluble MSP142 (FVO) expressed in E. coli offers excellent promise as a component of a vaccine against erythrocytic-stage falciparum malaria.


Molecular and Biochemical Parasitology | 2003

Development and pre-clinical analysis of a Plasmodium falciparum Merozoite Surface Protein-142 malaria vaccine

Evelina Angov; Barbara M. Aufiero; Ann Marie Turgeon; Michel Van Handenhove; Christian Ockenhouse; Kent E. Kester; Douglas S. Walsh; Jana S. McBride; Marie-Claude Dubois; Joe Cohen; J.David Haynes; Kenneth H. Eckels; D.Gray Heppner; W.Ripley Ballou; Carter Diggs; Jeffrey A. Lyon

Merozoite Surface Protein-1(42) (MSP-1(42)) is a leading vaccine candidate against erythrocytic malaria parasites. We cloned and expressed Plasmodium falciparum MSP-1(42) (3D7 clone) in Escherichia coli. The antigen was purified to greater than 95% homogeneity by using nickel-, Q- and carboxy-methyl (CM)-substituted resins. The final product, designated Falciparum Merozoite Protein-1 (FMP1), had endotoxin levels significantly lower than FDA standards. It was structurally correct based on binding conformation-dependent mAbs, and was stable. Functional antibodies from rabbits vaccinated with FMP1 in Freunds adjuvant inhibited parasite growth in vitro and also inhibited secondary processing of MSP-1(42). FMP1 formulated with GlaxoSmithKline Biologicals (GSK) adjuvant, AS02A or alum was safe and immunogenic in rhesus (Macaca mulatta) monkeys.


Vaccine | 1999

Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein 1 (msp-119) and T helper epitopes of tetanus toxoid

Wendy A. Keitel; Kent E. Kester; Robert L. Atmar; A. C. White; N. Bond; Carolyn A. Holland; Urszula Krzych; Dupeh R. Palmer; Egan A; Carter Diggs; W.R. Ballou; Hall Bf; David C. Kaslow

The safety and immunogenicity of 2 yeast-derived, blood-stage malaria vaccines were evaluated in a phase l trial. Healthy adults were given 2 or 3 doses of alum-adsorbed vaccine containing the 19 kDa carboxy-terminal fragment of the merozoite surface protein-1 (MSP-1(19)) derived from the 3D7 or the FVO strain of Plasmodium falciparum fused to tetanus toxoid T-helper epitopes P30 and P2. The first 2 doses of MSP-1(19) were well tolerated. Hypersensitivity reactions occurred in 3 subjects after the third dose of MSP-1(19), including bilateral injection site reactions in 2 (one with generalized skin rash), and probable histamine-associated hypotension in 1. Serum antibody responses to MSP-1(19) occurred in 5/16, 9/16 and 0/8 subjects given 20 microg of MSP-1(19), 200 microg of MSP-1(19), and control vaccines (hepatitis B or Td), respectively. Both MSP-1(19) vaccines were immunogenic in humans, but changes in formulation will be necessary to improve safety and immunogenicity profiles.

Collaboration


Dive into the Carter Diggs's collaboration.

Top Co-Authors

Avatar

Lorraine Soisson

United States Agency for International Development

View shared research outputs
Top Co-Authors

Avatar

D. Gray Heppner

Walter Reed Army Institute of Research

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Evelina Angov

Walter Reed Army Institute of Research

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Kent E. Kester

Walter Reed Army Institute of Research

View shared research outputs
Top Co-Authors

Avatar

Sheetij Dutta

Walter Reed Army Institute of Research

View shared research outputs
Top Co-Authors

Avatar

David E. Lanar

Walter Reed Army Institute of Research

View shared research outputs
Top Co-Authors

Avatar

Fouzia Farooq

Naval Medical Research Center

View shared research outputs
Top Co-Authors

Avatar

Harini Ganeshan

Naval Medical Research Center

View shared research outputs
Researchain Logo
Decentralizing Knowledge