New approaches to pre-erythrocytic malaria vaccination

Malaria is an infectious parasitic disease and a global threat responsible for an estimated 200 million cases and half a million deaths every year. Although progress has been made in recent years with a number of vaccines advancing into later stages of clinical trials, a vaccine with both high effic...

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Main Author: Mukhopadhyay, E
Other Authors: Salman, A
Format: Thesis
Language:English
Published: 2021
Subjects:
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author Mukhopadhyay, E
author2 Salman, A
author_facet Salman, A
Mukhopadhyay, E
author_sort Mukhopadhyay, E
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description Malaria is an infectious parasitic disease and a global threat responsible for an estimated 200 million cases and half a million deaths every year. Although progress has been made in recent years with a number of vaccines advancing into later stages of clinical trials, a vaccine with both high efficacy and durability still remains a target to achieve. This thesis presents the results of pre-clinical studies performed with the aim to obtain an improved version of the existing R21 vaccine capable of enhancing immunogenicity, protective efficacy and durability. With this aim, a set of novel R21 variants were designed exploring all immunogenic regions of the Plasmodium falciparum circumsporozoite protein in a VLP vaccine platform. Along with creating new variants, an alternative strategy of using pre-formed immune complexes consisting of R21 complexed with monoclonal antibody 2A10 to the central NANP repeats has been explored. With this strategy already in use for animal vaccines, promising published results obtained with Zika virus, and still unexplored for parasitic infections, I considered to apply this approach to malaria and have obtained promising results. Glycans linked to parasitic surface proteins remain relatively less explored in comparison to proteins and are capable of eliciting immune response that might hold protective potential. With this aim, the last results chapter of this thesis describes results obtained from using sporozoite surface specific glycan alpha- galactose as a vaccine candidate.
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spelling oxford-uuid:73a50303-1634-425c-8780-c2690b8b424f2022-04-07T08:27:41ZNew approaches to pre-erythrocytic malaria vaccinationThesishttp://purl.org/coar/resource_type/c_db06uuid:73a50303-1634-425c-8780-c2690b8b424fMalaria vaccineEnglishHyrax Deposit2021Mukhopadhyay, ESalman, AHill, AMalaria is an infectious parasitic disease and a global threat responsible for an estimated 200 million cases and half a million deaths every year. Although progress has been made in recent years with a number of vaccines advancing into later stages of clinical trials, a vaccine with both high efficacy and durability still remains a target to achieve. This thesis presents the results of pre-clinical studies performed with the aim to obtain an improved version of the existing R21 vaccine capable of enhancing immunogenicity, protective efficacy and durability. With this aim, a set of novel R21 variants were designed exploring all immunogenic regions of the Plasmodium falciparum circumsporozoite protein in a VLP vaccine platform. Along with creating new variants, an alternative strategy of using pre-formed immune complexes consisting of R21 complexed with monoclonal antibody 2A10 to the central NANP repeats has been explored. With this strategy already in use for animal vaccines, promising published results obtained with Zika virus, and still unexplored for parasitic infections, I considered to apply this approach to malaria and have obtained promising results. Glycans linked to parasitic surface proteins remain relatively less explored in comparison to proteins and are capable of eliciting immune response that might hold protective potential. With this aim, the last results chapter of this thesis describes results obtained from using sporozoite surface specific glycan alpha- galactose as a vaccine candidate.
spellingShingle Malaria vaccine
Mukhopadhyay, E
New approaches to pre-erythrocytic malaria vaccination
title New approaches to pre-erythrocytic malaria vaccination
title_full New approaches to pre-erythrocytic malaria vaccination
title_fullStr New approaches to pre-erythrocytic malaria vaccination
title_full_unstemmed New approaches to pre-erythrocytic malaria vaccination
title_short New approaches to pre-erythrocytic malaria vaccination
title_sort new approaches to pre erythrocytic malaria vaccination
topic Malaria vaccine
work_keys_str_mv AT mukhopadhyaye newapproachestopreerythrocyticmalariavaccination