Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein

Kothari, Neha; Genschmer, Kristopher R.; Kothari, Sudeep; Kim, Jeong Ah; Briles, David E.; Rhee, Dong Kwon; Carbis, Rodney

doi:10.1016/j.vaccine.2014.08.041

Cited by 9 publications

(12 citation statements)

References 25 publications

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“…Equal volumes of serum from each mouse in each group were pooled. The 10 week serum pools from conjugate vaccinated mice and hyperimmune standard serum raised against families 1 and 2 (Ab Frountier) were assayed by ELISA on plates coated with PspA family 1 or PspA family 2 as previously described [4]. All serum pools were also assayed for IgG subclass, ELISA plates were coated with Vi or PspA and serum dilutions added as previously described [4].…”

Section: Cross-reactivity Of Anti-pspa Response and Anti-vi And Anti-mentioning

confidence: 99%

“…The 10 week serum pools from conjugate vaccinated mice and hyperimmune standard serum raised against families 1 and 2 (Ab Frountier) were assayed by ELISA on plates coated with PspA family 1 or PspA family 2 as previously described [4]. All serum pools were also assayed for IgG subclass, ELISA plates were coated with Vi or PspA and serum dilutions added as previously described [4]. HRP-conjugated goat anti-mouse IgG1, IgG2a, IgG2b and IgG3 (Southern Biotech) were added to the appropriate wells and the remainder of the assay performed as per the anti-PspA ELISA.…”

Section: Cross-reactivity Of Anti-pspa Response and Anti-vi And Anti-mentioning

confidence: 99%

“…The Vi-PspA conjugates used in this study were conjugates 3 and 8 described previously [4], briefly conjugate 3 was made of PspA family 1 clade 2 and had a Vi:PspA ratio of 1.39 and conjugate 8 used PspA family 2 clade 3 and had a Vi:PspA ratio of 0.99. The vaccine doses are summarized in Table 1.…”

Section: Vaccination and Challenge Of Micementioning

confidence: 99%

“…The high cost of these vaccines is related to the large number of serotypes in the vaccines (7 to 23), additionally manufacture and formulation, particularly of the conjugate vaccines is complex. To address these issues we are developing a cross-protective non serotype dependent vaccine using PspA as the target protective antigen [4].…”

Section: Introductionmentioning

confidence: 99%

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A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi

Kothari

Choi

et al. 2015

Vaccine

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Section: Cross-reactivity Of Anti-pspa Response and Anti-vi And Anti-mentioning

confidence: 99%

Section: Cross-reactivity Of Anti-pspa Response and Anti-vi And Anti-mentioning

confidence: 99%

Section: Vaccination and Challenge Of Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi

Kothari

Choi

et al. 2015

Vaccine

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“…While serotype‐specific antibodies against capsular polysaccharides are a main mechanism of immune protection, a number of conserved pneumococcal proteins with immunogenic properties have been identified, including detoxified pneumolysin (dPly) and pneumococcal surface protein A (PspA) 10, 11, 12. Pneumolysin is a cytolysin produced by S. pneumoniae that enables the bacteria to penetrate the host's physical defences through its cytotoxic effect on epithelial cells, thus facilitating carriage and disease 13.…”

Section: Introductionmentioning

confidence: 99%

Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea

Francis

Richmond

Strickland

et al. 2016

Clinical and Experimental Immunology

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SummaryIn areas where Streptococcus pneumoniae is highly endemic, infants experience very early pneumococcal colonization of the upper respiratory tract, with carriage often persisting into adulthood. We aimed to explore whether newborns in high‐risk areas have pre‐existing pneumococcal‐specific cellular immune responses that may affect early pneumococcal acquisition. Cord blood mononuclear cells (CBMC) of 84 Papua New Guinean (PNG; high endemic) and 33 Australian (AUS; low endemic) newborns were stimulated in vitro with detoxified pneumolysin (dPly) or pneumococcal surface protein A (PspA; families 1 and 2) and compared for cytokine responses. Within the PNG cohort, associations between CBMC dPly and PspA‐induced responses and pneumococcal colonization within the first month of life were studied. Significantly higher PspA‐specific interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α, interleukin (IL)‐5, IL‐6, IL‐10 and IL‐13 responses, and lower dPly‐IL‐6 responses were produced in CBMC cultures of PNG compared to AUS newborns. Higher CBMC PspA‐IL‐5 and PspA‐IL‐13 responses correlated with a higher proportion of cord CD4 T cells, and higher dPly‐IL‐6 responses with a higher frequency of cord antigen‐presenting cells. In the PNG cohort, higher PspA‐specific IL‐5 and IL‐6 CBMC responses were associated independently and significantly with increased risk of earlier pneumococcal colonization, while a significant protective effect was found for higher PspA‐IL‐10 CBMC responses. Pneumococcus‐specific cellular immune responses differ between children born in pneumococcal high versus low endemic settings, which may contribute to the higher risk of infants in high endemic settings for early pneumococcal colonization, and hence disease.

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Glycoconjugate vaccines against Salmonella enterica serovars and Shigella species: existing and emerging methods for their analysis

et al. 2021

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The global spread of enteric disease, the increasingly limited options for antimicrobial treatment and the need for effective eradication programs have resulted in an increased demand for glycoconjugate enteric vaccines, made with carbohydrate-based membrane components of the pathogen, and their precise characterisation. A set of physico-chemical and immunological tests are employed for complete vaccine characterisation and to ensure their consistency, potency, safety and stability, following the relevant World Health Organization and Pharmacopoeia guidelines. Variable requirements for analytical methods are linked to conjugate structure, carrier protein nature and size and O-acetyl content of polysaccharide. We investigated a key stability-indicating method which measures the percent free saccharide of Salmonella enterica subspecies enterica serovar Typhi capsular polysaccharide, by detergent precipitation, depolymerisation and HPAEC-PAD quantitation. Together with modern computational approaches, a more precise design of glycoconjugates is possible, allowing for improvements in solubility, structural conformation and stability, and immunogenicity of antigens, which may be applicable to a broad spectrum of vaccines. More validation experiments are required to establish the most effective and suitable methods for glycoconjugate analysis to bring uniformity to the existing protocols, although the need for product-specific approaches will apply, especially for the more complex vaccines. An overview of current and emerging analytical approaches for the characterisation of vaccines against Salmonella Typhi and Shigella species is described in this paper. This study should aid the development and licensing of new glycoconjugate vaccines aimed at the prevention of enteric diseases.

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Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein

Cited by 9 publications

References 25 publications

A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi

A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi

Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea

Glycoconjugate vaccines against Salmonella enterica serovars and Shigella species: existing and emerging methods for their analysis

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