Intranasal immunization with outer membrane vesicle pertussis vaccine confers broad protection through mucosal IgA and Th17 responses

Raeven, René H. M.; Rockx-Brouwer, Dedeke; Kanojia, Gaurav; Maas, Larissa van der; Bindels, Tim H E; Have, Rimko ten; Riet, Elly van; Metz, Bernard; Kersten, Gideon

doi:10.1038/s41598-020-63998-2

Cited by 48 publications

(60 citation statements)

References 54 publications

(87 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7). (58). Subcutaneous and IN vaccination with omvPV polarized a Th1/Th17 response, which is also seen with both natural infection and the whole cell vaccine administration (58)(59)(60).…”

Section: Discussionmentioning

confidence: 94%

“…(58). Subcutaneous and IN vaccination with omvPV polarized a Th1/Th17 response, which is also seen with both natural infection and the whole cell vaccine administration (58)(59)(60). A substantial number of studies highlight the correlation between a Th1/Th17 immune response and long-term protection (44,60,61).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies demonstrated the induction of strong mucosal immune responses after intranasal immunization with formalin-inactivated whole cell pertussis vaccine (WCV) in adults and oral vaccination using heat inactivated WCV in infants (15,16). A recent preclinical mucosal vaccination study using a novel adjuvant (LP-GMP) combined with an acellular vaccine as well as an additional study using an outer membrane vesicles of pertussis vaccine (omvPV) demonstrated that intranasal (IN) immunization with a pertussis vaccine can confer protection from B. pertussis challenge (17,18). A live attenuated vaccine, BPZE1, has also exhibited protection in preclinical models and has progressed to clinical trials (19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intranasal Immunization with Acellular Pertussis Vaccines Results in Long-Term Immunity to Bordetella pertussis in Mice

et al. 2021

View full text Add to dashboard Cite

Bordetella pertussis colonizes the respiratory mucosa of humans, inducing an immune response seeded in the respiratory tract. An individual, once convalescent, exhibits long-term immunity to the pathogen. Current acellular pertussis (aP) vaccines do not induce the long-term immune response observed after natural infection in humans. In this study, we evaluated the durability of protection from intranasal (IN) pertussis vaccines in mice. Mice that convalesced from B. pertussis infection served as a control group. Mice were immunized with a mock vaccine (PBS), aP only, or an aP base vaccine combined with one of the following adjuvants: alum, curdlan, or purified whole glucan particle (IRI-1501). We utilized two study designs: short-term (challenged 35 days post-priming vaccination) and long-term (challenged six months post-boost). The short-term study demonstrated that immunization with IN vaccine candidates decreased bacterial burden in the respiratory tract, reduced markers of inflammation, and induced significant serum and lung antibody titers. In the long-term study, protection from bacterial challenge mirrored the results observed in the short-term challenge study. Immunization with pertussis antigens alone was surprisingly protective in both models; however, the alum and IRI-1501 adjuvants induced significant B. pertussis specific IgG antibodies in both the serum and lung, and increased numbers of anti-B. pertussis IgG secreting plasma cells in the bone marrow. Our data indicate that humoral responses induced by the IN vaccines correlated with protection, suggesting that long-term antibody responses can be protective.

show abstract

“…7). (58). Subcutaneous and IN vaccination with omvPV polarized a Th1/Th17 response, which is also seen with both natural infection and the whole cell vaccine administration (58)(59)(60).…”

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intranasal Immunization with Acellular Pertussis Vaccines Results in Long-Term Immunity to Bordetella pertussis in Mice

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Spots were counted with an AID iSpot reader (Autoimmun Diagnostika, Strassberg, Germany) and indicated as antibody-secreting cells (ASC) per 5 × 10 5 cells. For analysis of memory B-cells, splenocytes were stimulated to induce differentiation into antibody-secreting cells as described previously [ 21 ]. The amounts of OMV, BrkA and Vag8-specific ASC were subsequently determined by using the same ELISpot method, only here 1 × 10 5 stimulated cells were added to the coated plates.…”

Section: Methodsmentioning

confidence: 99%

“…Advantages of OMV vaccines are that they contain a broad variety of antigens in their natural conformation, have the perfect size for uptake by most antigen presenting cells [ 16 ], and hold intrinsic adjuvants such as endotoxin, or lipo-polysaccharide (LPS), as well as other pathogen-associated molecular patterns [ 14 , 17 ]. Immunization with omvPV provides protection against B. pertussis colonization in the lungs of mice [ 18 , 19 , 20 , 21 ]. In contrast to the acPV-induced Th2 immunity, omvPV mainly induces systemic Th1/Th17 immunity, next to Th2 responses [ 19 , 20 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Virulence Proteins in Protection Conferred by Bordetella pertussis Outer Membrane Vesicle Vaccines

Raeven¹,

Vlies²,

Salverda³

et al. 2020

Vaccines

Self Cite

View full text Add to dashboard Cite

The limited protective immunity induced by acellular pertussis vaccines demands development of novel vaccines that induce broader and longer-lived immunity. In this study, we investigated the protective capacity of outer membrane vesicle pertussis vaccines (omvPV) with different antigenic composition in mice to gain insight into which antigens contribute to protection. We showed that total depletion of virulence factors (bvg(-) mode) in omvPV led to diminished protection despite the presence of high antibody levels. Antibody profiling revealed overlap in humoral responses induced by vaccines in bvg(-) and bvg(+) mode, but the potentially protective responses in the bvg(+) vaccine were mainly directed against virulence-associated outer membrane proteins (virOMPs) such as BrkA and Vag8. However, deletion of either BrkA or Vag8 in our outer membrane vesicle vaccines did not affect the level of protection. In addition, the vaccine-induced immunity profile, which encompasses broad antibody and mixed T-helper 1, 2 and 17 responses, was not changed. We conclude that the presence of multiple virOMPs in omvPV is crucial for protection against Bordetella pertussis. This protective immunity does not depend on individual proteins, as their absence or low abundance can be compensated for by other virOMPs.

show abstract

Outer membrane vesicles as a platform for the discovery of antibodies to bacterial pathogens

Lei,

Azmat,

Henry

et al. 2024

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

Bacterial outer membrane vesicles (OMVs) are nanosized spheroidal particles shed by gram-negative bacteria that contain biomolecules derived from the periplasmic space, the bacterial outer membrane, and possibly other compartments. OMVs can be purified from bacterial culture supernatants, and by genetically manipulating the bacterial cells that produce them, they can be engineered to harbor cargoes and/or display molecules of interest on their surfaces including antigens that are immunogenic in mammals. Since OMV bilayer-embedded components presumably maintain their native structures, OMVs may represent highly useful tools for generating antibodies to bacterial outer membrane targets. OMVs have historically been utilized as vaccines or vaccine constituents. Antibodies that target bacterial surfaces are increasingly being explored as antimicrobial agents either in unmodified form or as targeting moieties for bactericidal compounds. Here, we review the properties of OMVs, their use as immunogens, and their ability to elicit antibody responses against bacterial antigens. We highlight antigens from bacterial pathogens that have been successfully targeted using antibodies derived from OMV-based immunization and describe opportunities and limitations for OMVs as a platform for antimicrobial antibody development. Key points • Outer membrane vesicles (OMVs) of gram-negative bacteria bear cell-surface molecules • OMV immunization allows rapid antibody (Ab) isolation to bacterial membrane targets • Review and analysis of OMV-based immunogens for antimicrobial Ab development

show abstract

Intranasal immunization with outer membrane vesicle pertussis vaccine confers broad protection through mucosal IgA and Th17 responses

Cited by 48 publications

References 54 publications

Intranasal Immunization with Acellular Pertussis Vaccines Results in Long-Term Immunity to Bordetella pertussis in Mice

Intranasal Immunization with Acellular Pertussis Vaccines Results in Long-Term Immunity to Bordetella pertussis in Mice

The Role of Virulence Proteins in Protection Conferred by Bordetella pertussis Outer Membrane Vesicle Vaccines

Outer membrane vesicles as a platform for the discovery of antibodies to bacterial pathogens

Contact Info

Product

Resources

About