Isotype switching: Mouse IgG3 constant region drives increased affinity for polysaccharide antigens

Harmer, Nicholas J.; Chahwan, Richard

doi:10.1080/21505594.2016.1193278

Cited by 16 publications

(16 citation statements)

References 34 publications

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“…5 ). This distinctive response is noteworthy given that IgG3 is a common subclass among bacterial oligosaccharide-specific antibody responses in mice 37 – 39 and given that we designed our mimetic to appear foreign to the immune system 5 . We therefore interpreted these results as suggesting that the Trianni mouse immune system sensed our glycoconjugate as a bacterial polysaccharide, possibly aided by its formulation in a TLR4 agonist adjuvant.…”

Section: Discussionmentioning

confidence: 99%

A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies

Bruxelle

Kirilenko

Trattnig

et al. 2021

Sci Rep

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The occurrence of oligomannose-specific broadly neutralizing antibodies (bnAbs) has spurred efforts to develop immunogens that can elicit similar antibodies. Here, we report on the antigenicity and immunogenicity of a CRM197-conjugate of a previously reported oligomannose mimetic. Oligomannose-specific bnAbs that are less dependent on interactions with the HIV envelope protein sequence showed strong binding to the glycoconjugates, with affinities approximating those reported for their cognate epitope. The glycoconjugate is also recognized by inferred germline precursors of oligomannose-specific bnAbs, albeit with the expected low avidity, supporting its potential as an immunogen. Immunization of human-antibody transgenic mice revealed that only a TLR4-stimulating adjuvant formulation resulted in antibodies able to bind a panel of recombinant HIV trimers. These antibodies bound at relatively modest levels, possibly explaining their inability to neutralize HIV infectivity. Nevertheless, these findings contribute further to understanding conditions for eliciting HIV-cross-reactive oligomannose-specific antibodies and inform on next steps for improving on the elicited response.

show abstract

Section: Discussionmentioning

confidence: 99%

A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies

Bruxelle

Kirilenko

Trattnig

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…IgG3 was the only subclass induced by prime/boost vaccination that displayed higher binding levels than those responses in the serum from infected mice. It is the only IgG subclass that is T cell independent and primarily is targeted against carbohydrates and repeating protein aggregates [ 54 – 56 ]. Studies have previously indicated that IgG3 subclass antibodies were the predominant anti-E2 glycoprotein response in mice vaccinated with CHIKV VLP and appeared shortly after vaccination [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have previously indicated that IgG3 subclass antibodies were the predominant anti-E2 glycoprotein response in mice vaccinated with CHIKV VLP and appeared shortly after vaccination [ 57 ]. IgG2b antibodies work with IgG3 in the early T cell independent response but function to bring early Fc γ R-mediated effector functions [ 56 ]. This partnership could explain why even if IgG3 primarily binds to E2 epitopes the expression is diminished at 7 dpi while IgG2b is elevated in order to direct ADCC and CDC functional responses.…”

Section: Discussionmentioning

confidence: 99%

Non-replicating adenovirus based Mayaro virus vaccine elicits protective immune responses and cross protects against other alphaviruses

et al. 2021

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Mayaro virus (MAYV) is an alphavirus endemic to South and Central America associated with sporadic outbreaks in humans. MAYV infection causes severe joint and muscle pain that can persist for weeks to months. Currently, there are no approved vaccines or therapeutics to prevent MAYV infection or treat the debilitating musculoskeletal inflammatory disease. In the current study, a prophylactic MAYV vaccine expressing the complete viral structural polyprotein was developed based on a non-replicating human adenovirus V (AdV) platform. Vaccination with AdV-MAYV elicited potent neutralizing antibodies that protected WT mice against MAYV challenge by preventing viremia, reducing viral dissemination to tissues and mitigating viral disease. The vaccine also prevented viral-mediated demise in IFN⍺R1-/- mice. Passive transfer of immune serum from vaccinated animals similarly prevented infection and disease in WT mice as well as virus-induced demise of IFN⍺R1-/- mice, indicating that antiviral antibodies are protective. Immunization with AdV-MAYV also generated cross-neutralizing antibodies against two related arthritogenic alphaviruses–chikungunya and Una viruses. These cross-neutralizing antibodies were protective against lethal infection in IFN⍺R1-/- mice following challenge with these heterotypic alphaviruses. These results indicate AdV-MAYV elicits protective immune responses with substantial cross-reactivity and protective efficacy against other arthritogenic alphaviruses. Our findings also highlight the potential for development of a multi-virus targeting vaccine against alphaviruses with endemic and epidemic potential in the Americas.

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“…4). This distinctive response is noteworthy given that IgG3 is a common subclass among bacterial oligosaccharide-speci c antibody responses in mice [34][35][36] and given that we designed our mimetic to appear foreign to the immune system 5 . We therefore interpreted these results as suggesting that the Trianni mouse immune system sensed our glycoconjugate as a bacterial polysaccharide, possibly aided by its formulation in a TLR4 agonist adjuvant.…”

Section: Discussionmentioning

confidence: 99%

A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies

Bruxelle

Kirilenko

Trattnig

et al. 2021

Preprint

View full text Add to dashboard Cite

The occurrence of oligomannose-specific broadly neutralizing antibodies (bnAbs) has spurred efforts to develop immunogens that can elicit similar antibodies. Here, we report on the antigenicity and immunogenicity of a CRM197-conjugate of a previously reported oligomannose mimetic. Oligomannose-specific bnAbs that are less dependent on interactions with the HIV envelope protein sequence showed strong binding to the glycoconjugates, with affinities approximating those reported for their cognate epitope. The glycoconjugate is also recognized by germline precursors of oligomannose-specific bnAbs, albeit with the expected low avidity, supporting its potential as an immunogen. Immunization of human-antibody transgenic mice revealed that only a TLR4-stimulating adjuvant formulation evoked antibodies able to bind a panel of recombinant HIV trimers. These antibodies bound at relatively modest levels, likely explaining their inability to neutralize HIV infectivity. Nevertheless, these findings contribute further to understanding conditions for eliciting HIV-cross-reactive oligomannose-specific antibodies and inform on next steps for improving on the elicited response.

show abstract

Isotype switching: Mouse IgG3 constant region drives increased affinity for polysaccharide antigens

Cited by 16 publications

References 34 publications

A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies

A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies

Non-replicating adenovirus based Mayaro virus vaccine elicits protective immune responses and cross protects against other alphaviruses

A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies

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