Malaria vaccine candidate based on Duffy-binding protein elicits strain transcending functional antibodies in a Phase I trial

Reticulocyte invasion by requires interaction of the Duffy-binding protein (PvDBP) with host Duffy antigen receptor for chemokines (DARCs). The binding domain of PvDBP maps to a cysteine-rich region referred to as region II (PvDBPII). Blocking this interaction offers a potential path to prevent bloo...

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Published in:npj vaccines 2018-09, Vol.3 (1), p.48-48, Article 48
Main Authors: Singh, Kavita, Mukherjee, Paushali, Shakri, Ahmad Rushdi, Singh, Ankita, Pandey, Gaurav, Bakshi, Meenakshi, Uppal, Geetanjali, Jena, Rajender, Rawat, Ankita, Kumar, Purnima, Bhardwaj, Rukmini, Yazdani, Syed Shams, Hans, Dhiraj, Mehta, Shantanu, Srinivasan, Ajay, Anil, K, Madhusudhan, R L, Patel, Jaya, Singh, Amit, Rao, Rajeshwar, Gangireddy, Santosh, Patil, Rudrappa, Kaviraj, Swarnendu, Singh, Sanjay, Carter, Darrick, Reed, Steve, Kaslow, David C, Birkett, Ashley, Chauhan, Virander S, Chitnis, Chetan E
Format: Article
Language:English
Subjects:
Antigens
Immunoglobulins
Malaria
Vaccines
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Summary:Reticulocyte invasion by requires interaction of the Duffy-binding protein (PvDBP) with host Duffy antigen receptor for chemokines (DARCs). The binding domain of PvDBP maps to a cysteine-rich region referred to as region II (PvDBPII). Blocking this interaction offers a potential path to prevent blood-stage growth and malaria. This forms the rationale for development of a vaccine based on PvDBPII. Here we report results of a Phase I randomized trial to evaluate the safety and immunogenicity of recombinant PvDBPII formulated with glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE). Thirty-six malaria-naive, healthy Indian male subjects aged 18-45 years were assigned into three cohorts corresponding to doses of 10, 25 and 50 µg of PvDBPII formulated with 5 µg of GLA-SE. Each cohort included nine PvDBPII/GLA-SE vaccinees and three hepatitis B control vaccine recipients. Each subject received the assigned vaccine intramuscularly on days 0, 28 and 56, and was followed up till day 180. No serious AE was reported and PvDBPII/GLA-SE was well-tolerated and safe. Analysis by ELISA showed that all three doses of PvDBPII elicited antigen-specific binding-inhibitory antibodies. The 50 µg dose elicited antibodies against PvDBPII that had the highest binding-inhibitory titres and were most persistent. Importantly, the antibody responses were strain transcending and blocked receptor binding of diverse PvDBP alleles. These results support further clinical development of PvDBPII/GLA-SE to evaluate efficacy against sporozoite or blood-stage challenge in controlled human malaria infection (CHMI) models and against natural challenge in malaria endemic areas.
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-018-0083-3