Sublingual immunisation with GBS serotype III capsular polysaccharide-tetanus toxoid conjugate vaccine induces systemic and mucosal antibody responses which are opsonophagocytic and inhibit GBS colonisation of vaginal epithelial cells

Yousif, Mohamed Deifallah; Felek, Arif; Saydam, Manolya; Wilson, Seanette; Murdan, Sudaxshina; Mawas, Fatme

doi:10.1016/j.vaccine.2022.08.064

Cited by 2 publications

(4 citation statements)

References 60 publications

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“…Further, selecting the appropriate adjuvant for the required immune response will be important, especially should any correlates of protection be uncovered in the coming years. Studies have shown that the sublingual route with CTB or heat-labile toxin can generate IgA at mucosal sites and serum IgG to protective levels against other species of Streptococci [10,11]. Several studies have demonstrated intranasal immunization can generate a mucosal immune response against GAS [14,16,25], but ours is the first study to show that a response can also be generated through immunization with a subunit vaccine by the sublingual route, which has potential safety benefits over intranasal immunization.…”

Section: Discussionmentioning

confidence: 82%

“…In this study we used five weekly doses of vaccine as this had been shown in preliminary work and in a study of GBS vaccine mucosal delivery to mount good immune responses [11]. To assess the benefit of five doses for our combination vaccine, we tested sera and fecal samples for IgG and secreted IgA responses respectively after three and five immunizations.…”

Section: Discussionmentioning

confidence: 99%

“…An immune response at mucosal sites will be necessary to target these initial colonization and infection events. Studies have indicated that immunization at mucosal sites can lead to an effective immune response to bacterial antigens for several pathogens [10][11][12]. In a passive-protection study, mice were shown to be more significantly protected from intranasal challenge with GAS when it was co-administered with human salivary IgA than when it was co-administered with serum IgG or no treatment [13].…”

Section: Introductionmentioning

confidence: 99%

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Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model

Shaw,

Remmington,

McKenzie

et al. 2023

Vaccines

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Group A Streptococcus (GAS) is a major human pathogen for which there is no licensed vaccine. To protect against infection, a strong systemic and mucosal immune response is likely to be necessary to prevent initial colonization and any events that might lead to invasive disease. A broad immune response will be necessary to target the varied GAS serotypes and disease presentations. To this end, we designed a representative panel of recombinant proteins to cover the stages of GAS infection and investigated whether mucosal and systemic immunity could be stimulated by these protein antigens. We immunized mice sublingually, intranasally and subcutaneously, then measured IgG and IgA antibody levels and functional activity through in vitro assays. Our results show that both sublingual and intranasal immunization in the presence of adjuvant induced both systemic IgG and mucosal IgA. Meanwhile, subcutaneous immunization generated only a serum IgG response. The antibodies mediated binding and killing of GAS cells and blocked binding of GAS to HaCaT cells, particularly following intranasal and subcutaneous immunizations. Further, antigen-specific assays revealed that immune sera inhibited cleavage of IL-8 by SpyCEP and IgG by Mac/IdeS. These results demonstrate that mucosal immunization can induce effective systemic and mucosal antibody responses. This finding warrants further investigation and optimization of humoral and cellular responses as a viable alternative to subcutaneous immunization for urgently needed GAS vaccines.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model

Shaw,

Remmington,

McKenzie

et al. 2023

Vaccines

Self Cite

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“…GBSV6 immunization induces maternal antibodies, which establish immunity against GBS in newborns for the prevention of newborn death. Additionally, mucosal immunity in the reproductive tract may reduce the risk of GBS transmission from the mother to the baby during pregnancy or at birth [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Immunization with Multiple Virulence Factors Provides Maternal and Neonatal Protection against Group B Streptococcus Serotypes

Wang,

Li,

et al. 2023

Vaccines

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Group B streptococcus (GBS) commonly colonizes the vaginal tract and is a leading cause of life-threatening neonatal infections and adverse pregnancy outcomes. No effective vaccine is clinically available. Conserved bacterial virulence factors, including those of GBS, have been employed as vaccine components. We investigated serotype-independent protection against GBS by intranasal immunization with six conserved GBS virulence factors (GBSV6). GBSV6 induced systemic and vaginal antibodies and T cell responses in mice. The immunity reduced mouse mortality and vaginal colonization by various GBS serotypes and protected newborn mice of immunized dams against GBS challenge. Intranasal GBSV6 immunization also provided long-lasting protective immunity and had advantages over intramuscular GBSV6 immunization regarding restricting vaginal GBS colonization. Our findings indicate that intranasal immunization targeting multiple conserved GBS virulence factors induces serotype-independent immunity, which protects against GBS infection systemically and vaginally in dams and prevents newborn death. The study presents valuable strategies for GBS vaccine development.

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Sublingual immunisation with GBS serotype III capsular polysaccharide-tetanus toxoid conjugate vaccine induces systemic and mucosal antibody responses which are opsonophagocytic and inhibit GBS colonisation of vaginal epithelial cells

Cited by 2 publications

References 60 publications

Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model

Mucosal Immunization Has Benefits over Traditional Subcutaneous Immunization with Group A Streptococcus Antigens in a Pilot Study in a Mouse Model

Immunization with Multiple Virulence Factors Provides Maternal and Neonatal Protection against Group B Streptococcus Serotypes

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