Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a unique asexual blood-stage malaria vaccine candidate because of its high conservation and essential biological function of binding to basigin on the erythrocyte surface. Recent studies by Barrett et al., Wang et al., and King et al., have brought RH5-based vaccine development a step forward based on a rational antigen design strategy.

01 Sep 2024·Cell

Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5

Article

Author: Lee, F Eun-Hyung ; Silk, Sarah E ; Tan, Joshua ; McHugh, Kirsty ; Tucker, Courtney ; Müller-Sienerth, Nicole ; Barrett, Jordan R ; Geraghty, Daniel E ; Doumbo, Safiatou ; Minassian, Angela M ; Traore, Boubacar ; Kayentao, Kassoum ; Kirtley, Payton J ; Pyo, Chul-Woo ; Cooper, Andrew J R ; Skinner, Jeff ; Crompton, Peter D ; Crosnier, Cécile ; Purser, Lauren ; Nguyen, Doan C ; Doumtabe, Didier ; Wright, Gavin J ; Diouf, Ababacar ; Long, Carole A ; Wilder, Brandon K ; Miura, Kazutoyo ; Zhao, Ming ; Li, Shanping ; Seder, Robert A ; Maciuszek, Maciej ; Ogwang, Rodney ; Higgins, Matthew K ; Farrell, Brendan ; Nielsen, Carolyn M ; Ongoiba, Aissata ; Wang, Lawrence T ; Draper, Simon J

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is the most advanced blood-stage malaria vaccine candidate and is being evaluated for efficacy in endemic regions, emphasizing the need to study the underlying antibody response to RH5 during natural infection, which could augment or counteract responses to vaccination. Here, we found that RH5-reactive B cells were rare, and circulating immunoglobulin G (IgG) responses to RH5 were short-lived in malaria-exposed Malian individuals, despite repeated infections over multiple years. RH5-specific monoclonal antibodies isolated from eight malaria-exposed individuals mostly targeted non-neutralizing epitopes, in contrast to antibodies isolated from five RH5-vaccinated, malaria-naive UK individuals. However, MAD8-151 and MAD8-502, isolated from two malaria-exposed Malian individuals, were among the most potent neutralizers out of 186 antibodies from both cohorts and targeted the same epitopes as the most potent vaccine-induced antibodies. These results suggest that natural malaria infection may boost RH5-vaccine-induced responses and provide a clear strategy for the development of next-generation RH5 vaccines.

07 Sep 2023·Vaccine

An Advax-CpG adjuvanted recombinant H5 hemagglutinin vaccine protects mice against lethal influenza infection.

Article

Author: Bart Tarbet, E ; Petrovsky, Nikolai ; Hurst, Brett L ; Honda-Okubo, Yoshikazu

There is a major unmet need for strategies to improve the immunogenicity of vaccines to protect against highly pathogenic avian influenza strains with pandemic potential. This study tested the ability of adjuvants based on delta inulin (Advax™) alone or combined with a TLR9 agonist (Advax-CpG™) to enhance the immunogenicity of recombinant H5 hemagglutinin antigen expressed in insect cells (rH5HA) to protect mice against lethal influenza infection. The Advax-adjuvanted rH5HA induced high serum hemagglutination inhibition activity, as well as Th1 and Th2 cytokine secreting CD4 and CD8 T cells. Immunization protected mice against a lethal heterosubtypic H5N1 virus challenge. Mice immunized with an Advax-adjuvanted rHA2 stem antigen prepared by enzymatic cleavage of rH5HA produced serum antibodies devoid of hemagglutination inhibition activity, but these anti-HA2 antibodies were nevertheless able to transfer protection against lethal H1N1 or H3N2 infections to naïve mice. We hypothesize that the enhanced protection afforded by Advax-adjuvanted rH5HA may be mediated by the combination of neutralizing antibodies directed at the HA head, anti-HA2 stem antibodies plus memory CD4 + and CD8 + T cells. This outcome supports further development of the Advax-adjuvanted rH5 pandemic influenza vaccine platform.

100 Deals associated with NE-rH5 vaccine(BlueWillow Biologics)

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Indication	Highest Phase	Country/Location	Organization	Date
Influenza in Birds	Phase 1	US	BlueWillow Biologics, Inc.	30 Jan 2022

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