Heterotypic interactions drive antibody synergy against a malaria vaccine candidate.
Nat Commun
; 13(1): 933, 2022 02 17.
Article
em En
| MEDLINE
| ID: mdl-35177602
ABSTRACT
Understanding mechanisms of antibody synergy is important for vaccine design and antibody cocktail development. Examples of synergy between antibodies are well-documented, but the mechanisms underlying these relationships often remain poorly understood. The leading blood-stage malaria vaccine candidate, CyRPA, is essential for invasion of Plasmodium falciparum into human erythrocytes. Here we present a panel of anti-CyRPA monoclonal antibodies that strongly inhibit parasite growth in in vitro assays. Structural studies show that growth-inhibitory antibodies bind epitopes on a single face of CyRPA. We also show that pairs of non-competing inhibitory antibodies have strongly synergistic growth-inhibitory activity. These antibodies bind to neighbouring epitopes on CyRPA and form lateral, heterotypic interactions which slow antibody dissociation. We predict that such heterotypic interactions will be a feature of many immune responses. Immunogens which elicit such synergistic antibody mixtures could increase the potency of vaccine-elicited responses to provide robust and long-lived immunity against challenging disease targets.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Antiprotozoários
/
Proteínas de Protozoários
/
Malária Falciparum
/
Vacinas Antimaláricas
/
Anticorpos Monoclonais
/
Antígenos de Protozoários
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article