Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan

Younis, Brima M.; Osman, Mohamed; Khalil, Eltahir Awad Gasim; Santoro, Francesco; Furini, Simone; Wiggins, Rebecca; Keding, Ada; Carraro, Monica; Musa, A.; Abdarahaman, Mujahid A.A.; Mandefield, Laura; Bland, Martin; Aebischer, Toni; Gabe, Rhian; Layton, Alison; Lacey, Charles; Kaye, Paul M.; Musa, Ahmed

doi:10.1016/j.ymthe.2021.03.020

Cited by 37 publications

(34 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to these clinical outcomes, we will also conduct in depth immune profiling using whole blood transcriptomics to evaluate vaccine-induced immunity and to determine whether there are biomarkers in blood that reflect either responsiveness to vaccine-induced cure or that predict self-cure. In our previously reported Phase 2a safety and immunogenicity study involving 24 patients 27 , we observed that immune modules associated with antigen presentation and macrophage function were significantly over-represented in patients that successful cleared their PKDL within 90 -120 days of vaccination. However, this study did not have a placebo control and so we were not able to determine whether these immune response differences were related to vaccine response or reflected patient heterogeneity.…”

Section: Discussionmentioning

confidence: 81%

“…Following external peer review of the data generated during LEISH1, a phase 2a study was funded in adults and adolescents with >six months PKDL. This trial successfully completed at the Dooka Centre for Tropical Medicine and the vaccine showed minimal adverse reactions in PKDL patients and induced potent innate and cell-mediated immune responses measured by whole-blood transcriptomics and ELISpot 27 .…”

Section: Rationale For a Therapeutic Cd8 + T Cell-inducing Vaccine Ag...mentioning

confidence: 99%

See 1 more Smart Citation

LEISH2b - A phase 2b study to assess the safety, efficacy, and immunogenicity of the Leishmania vaccine ChAd63-KH in post-kala azar dermal leishmaniasis

Lacey¹,

Musa²,

Khalil³

et al. 2022

Wellcome Open Res

Self Cite

View full text Add to dashboard Cite

Background: The leishmaniases are neglected tropical diseases caused by various Leishmania parasite species transmitted by sand flies. They comprise a number of systemic and cutaneous syndromes including kala-azar (visceral leishmaniasis, VL), cutaneous leishmaniasis (CL), and post-kala-azar dermal leishmaniasis (PKDL). The leishmaniases cause significant mortality (estimated 20 - 50,000 deaths annually), morbidity, psychological sequelae, and healthcare and societal costs. Treatment modalities remain difficult. E.g., East African PKDL requires 20 days of intravenous therapy, and frequently relapsing VL is seen in the setting of HIV and immunodeficiency. We developed a new therapeutic vaccine, ChAd63-KH for VL / CL / PKDL and showed it to be safe and immunogenic in a phase 1 trial in the UK, and in a phase 2a trial in PKDL patients in Sudan. Methods: This is a randomised double-blind placebo-controlled phase 2b trial to assess the therapeutic efficacy and safety of ChAd63-KH in patients with persistent PKDL in Sudan. 100 participants will be randomly assigned 1:1 to receive placebo or ChAd63-KH (7.5 x1010vp i.m.) at a single time point. Follow up is for 120 days after dosing and we will compare the clinical evolution of PKDL, as well as the humoral and cellular immune responses between the two arms. Discussion: Successful development of a therapeutic vaccine for leishmaniasis would have wide-ranging direct and indirect healthcare benefits that could be realized rapidly. For PKDL patients, an effective therapeutic vaccination used alone would have very significant clinical value, reducing the need for extensive hospitalization and chemotherapy. Combining vaccine with drug (immuno-chemotherapy) might significantly increase the effective life of new drugs, with lower dose / abbreviated regimens helping to limit the emergence of drug resistance. If therapeutic benefit of ChAd63-KH can be shown in PKDL further evaluation of the vaccine in other forms of leishmaniasis should be considered. Clinicaltrials.gov registration: NCT03969134.

show abstract

Section: Discussionmentioning

confidence: 81%

Section: Rationale For a Therapeutic Cd8 + T Cell-inducing Vaccine Ag...mentioning

confidence: 99%

LEISH2b - A phase 2b study to assess the safety, efficacy, and immunogenicity of the Leishmania vaccine ChAd63-KH in post-kala azar dermal leishmaniasis

Lacey¹,

Musa²,

Khalil³

et al. 2022

Wellcome Open Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…Immunochemotherapy may be second line treatment in chronic or refractory cases; the ChAd63-KH vaccine seems a suitable candidate to further build on previous experience with the autoclaved L. major vaccine ( Younis et al., 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Precision Medicine in Control of Visceral Leishmaniasis Caused by L. donovani

Zijlstra¹

2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Precision medicine and precision global health in visceral leishmaniasis (VL) have not yet been described and could take into account how all known determinants improve diagnostics and treatment for the individual patient. Precision public health would lead to the right intervention in each VL endemic population for control, based on relevant population-based data, vector exposures, reservoirs, socio-economic factors and other determinants. In anthroponotic VL caused by L. donovani, precision may currently be targeted to the regional level in nosogeographic entities that are defined by the interplay of the circulating parasite, the reservoir and the sand fly vector. From this 5 major priorities arise: diagnosis, treatment, PKDL, asymptomatic infection and transmission. These 5 priorities share the immune responses of infection with L. donovani as an important final common pathway, for which innovative new genomic and non-genomic tools in various disciplines have become available that provide new insights in clinical management and in control. From this, further precision may be defined for groups (e.g. children, women, pregnancy, HIV-VL co-infection), and eventually targeted to the individual level.

show abstract

“…The phase IIa safety and immunogenicity trial was conducted in Sudanese patients with persistent PKDL. ChAd63-KH vaccine showed minimal adverse reactions and induced potent innate and cell-mediated immune responses [350].…”

Section: Third-generation Vaccinementioning

confidence: 99%

Host–Pathogen Interaction in Leishmaniasis: Immune Response and Vaccination Strategies

Yasmin

Adhikary

Al-Ahdal

et al. 2022

Immuno

View full text Add to dashboard Cite

Leishmaniasis is a zoonotic and vector-borne infectious disease that is caused by the genus Leishmania belonging to the trypanosomatid family. The protozoan parasite has a digenetic life cycle involving a mammalian host and an insect vector. Leishmaniasisis is a worldwide public health problem falling under the neglected tropical disease category, with over 90 endemic countries, and approximately 1 million new cases and 20,000 deaths annually. Leishmania infection can progress toward the development of species–specific pathologic disorders, ranging in severity from self-healing cutaneous lesions to disseminating muco-cutaneous and fatal visceral manifestations. The severity and the outcome of leishmaniasis is determined by the parasite’s antigenic epitope characteristics, the vector physiology, and most importantly, the immune response and immune status of the host. This review examines the nature of host–pathogen interaction in leishmaniasis, innate and adaptive immune responses, and various strategies that have been employed for vaccine development.

show abstract

Safety and immunogenicity of ChAd63-KH vaccine in post-kala-azar dermal leishmaniasis patients in Sudan

Cited by 37 publications

References 55 publications

LEISH2b - A phase 2b study to assess the safety, efficacy, and immunogenicity of the Leishmania vaccine ChAd63-KH in post-kala azar dermal leishmaniasis

LEISH2b - A phase 2b study to assess the safety, efficacy, and immunogenicity of the Leishmania vaccine ChAd63-KH in post-kala azar dermal leishmaniasis

Precision Medicine in Control of Visceral Leishmaniasis Caused by L. donovani

Host–Pathogen Interaction in Leishmaniasis: Immune Response and Vaccination Strategies

Contact Info

Product

Resources

About