Humoral protection against mosquito bite-transmitted Plasmodium falciparum infection in humanized mice DOI Creative Commons

Brandon K. Sack,

Sebastian A. Mikolajczak,

Matthew Fishbaugher

и другие.

npj Vaccines, Год журнала: 2017, Номер 2(1)

Опубликована: Окт. 4, 2017

A malaria vaccine that prevents infection will be an important new tool in continued efforts of elimination, and such vaccines are under intense development for the major human parasite Plasmodium falciparum (Pf). Antibodies elicited by can block initial phases when sporozoites deposited into skin mosquito bite then target liver further development. However, there currently no standardized vivo preclinical models measure inhibitory activity antibody specificities against Pf sporozoite via bite. Here, we use liver-chimeric mice as a challenge model to assess prevention natural antibodies. We demonstrate these consistently infected with this combined passive transfer either monoclonal antibodies or polyclonal IgG from immune serum antibody-mediated blocking using bioluminescent imaging. This methodology is useful down-select functional investigate mechanisms correlates protection clinical trials, thereby informing rational optimization.

Язык: Английский

Malaria Vaccines: Recent Advances and New Horizons DOI Creative Commons
Simon J. Draper,

Brandon K. Sack,

C. Richter King

и другие.

Cell Host & Microbe, Год журнала: 2018, Номер 24(1), С. 43 - 56

Опубликована: Июль 1, 2018

The development of highly effective and durable vaccines against the human malaria parasites Plasmodium falciparum P. vivax remains a key priority. Decades endeavor have taught that achieving this goal will be challenging; however, recent innovation in vaccine research diverse pipeline novel candidates for clinical assessment provides optimism. With first-generation pre-erythrocytic aiming licensure coming years, it is important to reflect on how next-generation approaches can improve their success. Here we review latest seek prevent infection, disease, transmission highlight some major underlying immunological molecular mechanisms protection. synthesis rational antigen selection, immunogen design, immunization strategies induce quantitatively qualitatively improved immune effector offers promise sustained high-level

Язык: Английский

Процитировано

306

TRSP is dispensable for the Plasmodium pre-erythrocytic phase DOI Creative Commons
David Costa, Mónica Sá, Ana Rafaela Teixeira

и другие.

Scientific Reports, Год журнала: 2018, Номер 8(1)

Опубликована: Окт. 4, 2018

Abstract Plasmodium sporozoites deposited in the skin following a mosquito bite must migrate and invade blood vessels to complete their development liver. Once bloodstream, arrest liver sinusoids, but molecular determinants that mediate this specific homing are not yet genetically defined. Here we investigate involvement of thrombospondin-related sporozoite protein (TRSP) process using knockout berghei parasites vivo bioluminescence imaging mice. Resorting assay, trsp were found similar control parasites. Moreover, no defects establishment infection mice inoculation via intravenous cutaneous injection or bite. Accordingly, mutant also able successfully hepatocytes vitro . Altogether, these results suggest TRSP may have redundant role completion pre-erythrocytic phase malaria parasite. Nonetheless, identifying molecules with paramount roles could aid search for new antigens needed design protective vaccine against malaria.

Язык: Английский

Процитировано

235

A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein DOI
Joshua Tan,

Brandon K. Sack,

David Oyen

и другие.

Nature Medicine, Год журнала: 2018, Номер 24(4), С. 401 - 407

Опубликована: Март 19, 2018

Язык: Английский

Процитировано

206

Challenges and strategies for developing efficacious and long-lasting malaria vaccines DOI Creative Commons
James G. Beeson, Liriye Kurtovic, Carlota Dobaño

и другие.

Science Translational Medicine, Год журнала: 2019, Номер 11(474)

Опубликована: Янв. 9, 2019

New knowledge and strategies are emerging to enable the development of an efficacious long-lasting vaccine against malaria.

Язык: Английский

Процитировано

183

Glycoproteomics DOI Open Access
Ieva Bagdonaite, Stacy A. Malaker, Daniel A. Polasky

и другие.

Nature Reviews Methods Primers, Год журнала: 2022, Номер 2(1)

Опубликована: Июнь 23, 2022

Язык: Английский

Процитировано

164

Protein O-fucosylation: structure and function DOI
Bernadette C. Holdener, Robert S. Haltiwanger

Current Opinion in Structural Biology, Год журнала: 2019, Номер 56, С. 78 - 86

Опубликована: Янв. 27, 2019

Язык: Английский

Процитировано

126

Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites DOI Creative Commons
Scott E. Lindner, Kristian E. Swearingen, Melanie J. Shears

и другие.

Nature Communications, Год журнала: 2019, Номер 10(1)

Опубликована: Окт. 31, 2019

Abstract Plasmodium sporozoites are transmitted from infected mosquitoes to mammals, and must navigate the host skin vasculature infect liver. This journey requires distinct proteomes. Here, we report dynamic transcriptomes proteomes of both oocyst salivary gland in rodent-infectious yoelii parasites human-infectious falciparum parasites. The data robustly define mRNAs proteins that upregulated (UOS) or infectious (UIS) within glands, including many essential for sporozoite functions vector host. Moreover, find malaria use two overlapping, extensive, independent programs translational repression across maturation temporally regulate protein expression. Together with gene-specific validation experiments, these indicate waves implemented relieved at different times during maturation, migration infection, thus promoting their successful development vector-to-host transition.

Язык: Английский

Процитировано

123

Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are ineffective against malaria infection DOI Creative Commons
S.W. Scally, Rajagopal Murugan, Alexandre Bosch

и другие.

The Journal of Experimental Medicine, Год журнала: 2017, Номер 215(1), С. 63 - 75

Опубликована: Ноя. 22, 2017

Antibodies against the central repeat of Plasmodium falciparum (Pf) circumsporozoite protein (CSP) inhibit parasite activity and correlate with protection from malaria. However, humoral response to PfCSP C terminus (C-PfCSP) is less well characterized. Here, we describe B cell responses C-PfCSP European donors who underwent immunization live Pf sporozoites (PfSPZ Challenge) under chloroquine prophylaxis (PfSPZ-CVac), were protected controlled human malaria infection. Out 215 PfCSP-reactive monoclonal antibodies, only two unique antibodies specific for C-PfCSP, highlighting rare occurrence C-PfCSP–reactive cells in PfSPZ-CVac–induced protective immunity. These showed poor sporozoite binding weak inhibition traversal development, did not protect mice infection transgenic berghei sporozoites. Structural analyses demonstrated that one antibody interacts a polymorphic region overlapping T epitopes, suggesting variability may benefit escape cellular Our data identify important features underlying shortcomings as vaccine target.

Язык: Английский

Процитировано

97

Complete attenuation of genetically engineered Plasmodium falciparum sporozoites in human subjects DOI
James G. Kublin, Sebastian A. Mikolajczak,

Brandon K. Sack

и другие.

Science Translational Medicine, Год журнала: 2017, Номер 9(371)

Опубликована: Янв. 4, 2017

Immunization of humans with whole sporozoites confers complete, sterilizing immunity against malaria infection. However, achieving consistent safety while maintaining immunogenicity parasite vaccines remains a formidable challenge. We generated genetically attenuated Plasmodium falciparum (Pf) by deleting three genes expressed in the pre-erythrocytic stage (Pf p52-/p36-/sap1-). then tested and engineered GAP3KO) human volunteers. Pf GAP3KO were delivered to 10 volunteers using infected mosquito bites single exposure consisting 150 200 per subject. All subjects remained blood stage-negative developed inhibitory antibodies sporozoites. rodent parasites engendered protracted infectious sporozoite challenge mice. The results warrant further clinical testing its potential development into vaccine strain.

Язык: Английский

Процитировано

94

Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein DOI
Cherrelle Dacon,

Re’em Moskovitz,

Kristian E. Swearingen

и другие.

Science, Год журнала: 2025, Номер 387(6729)

Опубликована: Янв. 2, 2025

The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within Plasmodium falciparum circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses whole sporozoites, we identified a class of mAbs that cryptic PfCSP epitope is only exposed after cleavage subsequent pyroglutamylation (pGlu) newly formed N terminus. This pGlu-CSP not targeted by current anti-PfCSP included in licensed vaccines. MAD21-101, potent mAb this class, confers sterile protection Pf infection liver–chimeric mouse model. These findings reveal site vulnerability on sporozoite surface can be next-generation antimalarial interventions.

Язык: Английский

Процитировано

2