Potent Plasmablast-Derived Antibodies Elicited by the National Institutes of Health Dengue Vaccine

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art_MAGNANI_Potent_PlasmablastDerived_Antibodies_Elicited_by_the_National_Institutes_2017.PDF (595.33 KB)
Citações na Scopus
20
Tipo de produção
article
Data de publicação
2017
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMER SOC MICROBIOLOGY
Autores
MAGNANI, Diogo M.
RICCIARDI, Michael J.
GONZALEZ-NIETO, Lucas
PEDRENO-LOPEZ, Nuria
BAILEY, Varian K.
GUTMAN, Martin J.
MAXWELL, Helen S.
DOMINGUES, Aline
Citação
JOURNAL OF VIROLOGY, v.91, n.22, article ID UNSP e00867-17, 12p, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Exposure to dengue virus (DENV) is thought to elicit lifelong immunity, mediated by DENV-neutralizing antibodies (nAbs). However, Abs generated by primary infections confer serotype-specific protection, and immunity against other serotypes develops only after subsequent infections. Accordingly, the induction of these nAb responses acquired after serial DENV infections has been a long-sought-after goal for vaccination. Nonetheless, it is still unclear if tetravalent vaccines can elicit or recall nAbs. In this study, we have characterized the responses from a volunteer who had been previously exposed to DENV and was immunized with the live attenuated tetravalent vaccine Butantan-DV, developed by the NIH and Butantan Institute. Eleven days after vaccination, we observed an similar to 70-fold expansion of the plasmablast population. We generated 21 monoclonal Abs (MAbs) from singly sorted plasmablasts. These MAbs were the result of clonal expansions and had significant levels of somatic hypermutation (SHM). Nineteen MAbs (90.5%) neutralized at least one DENV serotype at concentrations of 1 mu g/ml or less; 6 of the 21 MAbs neutralized three or more serotypes. Despite the tetravalent composition of the vaccine, we observed a neutralization bias in the induced repertoire: DENV3 was targeted by 18 of the 19 neutralizing MAbs (nMAbs). Furthermore, the P3D05 nMAb neutralized DENV3 with extraordinary potency (concentration to achieve half-maximal neutralization [Neut(50)] = 0.03 mu g/ml). Thus, the Butantan-DV vaccine engendered a mature, antigen-selected B cell repertoire. Our results suggest that preexisting responses elicited by a previous DENV3 infection were recalled by immunization. IMPORTANCE The dengue epidemic presents a global public health challenge that causes widespread economic burden and remains largely unchecked by existing control strategies. Successful control of the dengue epidemic will require effective prophylactic and therapeutic interventions. Several vaccine clinical efficacy trials are approaching completion, and the chances that one or more live attenuated tetravalent vaccines (LATVs) will be introduced worldwide is higher than ever. While it is widely accepted that dengue virus (DENV)-neutralizing antibody (nAb) titers are associated with protection, the Ab repertoire induced by LATVs remain uncharacterized. Here, we describe the isolation of potent (Neut(50) < 0.1 mu g/ml) nAbs from a DENV-seropositive volunteer immunized with the tetravalent vaccine Butantan-DV, which is currently in phase III trials.
Palavras-chave
B cell, Butantan-DV, TV003, dengue, monoclonal antibodies, plasmablast, vaccines
URI
https://observatorio.fm.usp.br/handle/OPI/24207
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/19
Artigos e Materiais de Revistas Científicas - LIM/60
Artigos e Materiais de Revistas Científicas - ODS/03