Antibodies from malaria-exposed Malians generally interact additively or synergistically with human vaccine-induced RH5 antibodies
| Autor: | Kazutoyo Miura, David Pulido, Alex S. Huber, Simon J. Draper, Alexandra C. Willcox, Angela M. Minassian, Mahamadou Diakite, Lloyd D.W. King, Daniel G. W. Alanine, Jordan R. Barrett, Carole A. Long, Ababacar Diouf, Sarah E. Silk |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Adolescent medicine.drug_class Plasmodium falciparum Antibodies Protozoan Monoclonal antibody Mali General Biochemistry Genetics and Molecular Biology Article blood stage growth inhibition assay Antimalarials Young Adult vaccine parasitic diseases Malaria Vaccines medicine Humans Binding site Apical membrane antigen 1 Malaria Falciparum Child Aged biology Vaccination Antibody titer Antibodies Monoclonal Infant antibody interaction Middle Aged biology.organism_classification Virology Antibodies Neutralizing RH5 Polyclonal antibodies Child Preschool Immunoglobulin G biology.protein Female Antibody |
| Zdroj: | Cell Reports Medicine |
| ISSN: | 2666-3791 |
| Popis: | Summary Reticulocyte-binding protein homolog 5 (RH5) is a leading Plasmodium falciparum blood-stage vaccine candidate. Another possible candidate, apical membrane antigen 1 (AMA1), was not efficacious in malaria-endemic populations, likely due to pre-existing antimalarial antibodies that interfered with the activity of vaccine-induced AMA1 antibodies, as judged by in vitro growth inhibition assay (GIA). To determine how pre-existing antibodies interact with vaccine-induced RH5 antibodies, we purify total and RH5-specific immunoglobulin Gs (IgGs) from malaria-exposed Malians and malaria-naive RH5 vaccinees. Infection-induced RH5 antibody titers are much lower than those induced by vaccination, and RH5-specific IgGs show differences in the binding site between the two populations. In GIA, Malian polyclonal IgGs show additive or synergistic interactions with RH5 human monoclonal antibodies and overall additive interactions with vaccine-induced polyclonal RH5 IgGs. These results suggest that pre-existing antibodies will interact favorably with vaccine-induced RH5 antibodies, in contrast to AMA1 antibodies. This study supports RH5 vaccine trials in malaria-endemic regions. Graphical abstract Highlights RH5 IgG titers induced by infection are lower than those induced by RH5 vaccination Infection- and vaccine-induced RH5 IgGs have different specificity and avidity Infection- and vaccine-induced RH5 IgGs interact differently with RH5 mAbs Infection-induced IgGs generally do not reduce the activity of vaccine-induced IgGs Willcox et al. combine antibodies from malaria-exposed Malians and volunteers who received a reticulocyte-binding protein homolog 5 (RH5) vaccine. In P. falciparum growth inhibition assays, infection-induced IgGs generally do not reduce the neutralizing activity of vaccine-induced IgGs. These results suggest that RH5 vaccines will induce effective antibodies in malaria-endemic populations. |
| Databáze: | OpenAIRE |
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