Intradermally Administered Enterotoxigenic Escherichia coli Vaccine Candidate MecVax Induces Functional Serum Immunoglobulin G Antibodies against Seven Adhesins (CFA/I and CS1 through CS6) and Both Toxins (STa and LT).
Appl Environ Microbiol
; 88(4): e0213921, 2022 02 22.
Article
em En
| MEDLINE
| ID: mdl-34936832
ABSTRACT
There are no vaccines licensed for enterotoxigenic Escherichia coli (ETEC), a leading bacterial cause of children's diarrhea and travelers' diarrhea. MecVax, a multivalent E. coli vaccine candidate composed of two epitope- and structure-based polyvalent proteins (toxoid fusion 3xSTaN12S-mnLTR192G/L211A and colonization factor antigen [CFA]/I/II/IV multiepitope fusion antigen [MEFA]), is designed to induce broad antiadhesin and antitoxin antibodies against heterogeneous ETEC pathovars. When administered intraperitoneally or intramuscularly, MecVax was shown to induce antibodies against seven ETEC adhesins (CFA/I and CS1 to CS6) produced by ETEC pathovars that cause over 60% of ETEC-associated diarrheal cases and moderate-to-severe cases and both toxins (heat-labile toxin [LT] and heat-stable toxin [STa]) expressed by all ETEC strains. To further characterize the immunogenicity of this protein-based injectable subunit vaccine candidate and to explore other parenteral administration routes for the product, in this study we immunized mice intradermally (i.d.) with MecVax and measured antigen-specific antibody responses and further antibody functional activities against the adhesins and toxins targeted by the vaccine. Data showed that mice immunized i.d. with MecVax developed robust anti-CFA/I, CS1, CS2, CS3, CS4, CS5, CS6, LT and anti-STa IgG responses. Furthermore, antibodies derived from MecVax administered via the i.d. route inhibited the adherence of ETEC or E. coli strains expressing any of the seven target adhesins (CFA/I and CS1 to CS6) and neutralized the enterotoxicity of LT and STa. These results confirmed broad immunogenicity of MecVax and suggested that this multivalent ETEC subunit vaccine candidate can be effectively delivered via the i.d. route. IMPORTANCE ETEC is a leading bacterial cause of diarrhea in children living in developing countries and international travelers. Developing an effective vaccine for ETEC diarrhea has been hampered because of the challenges of virulence heterogeneity and the difficulties of inducing neutralizing antibodies against the key toxin STa. MecVax, a subunit vaccine candidate carrying two polyvalent protein antigens, for the first time induces functional antibodies against the most important ETEC adhesins, which are associated with a majority of diarrheal cases and moderate-to-severe cases, and also against the enterotoxicity of LT and more importantly STa, which plays a key role in children's diarrhea and travelers' diarrhea, potentially leading to the development of a truly effective ETEC vaccine. Data from this study may also indicate that this ETEC subunit vaccine can be administered effectively via the i.d. route, expanding clinical administration options for this vaccine product.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Toxinas Bacterianas
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Vacinas contra Escherichia coli
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Proteínas de Escherichia coli
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Infecções por Escherichia coli
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Escherichia coli Enterotoxigênica
Limite:
Animals
Idioma:
En
Revista:
Appl Environ Microbiol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos