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Article ; Online: Development of an Enzyme-Mediated, Site-Specific Method to Conjugate Toll-Like Receptor 2 Agonists onto Protein Antigens: Toward a Broadly Protective, Four Component, Group A Streptococcal Self-Adjuvanting Lipoprotein-Fusion Combination Vaccine.

Xu, Zhenghui / Rivera-Hernandez, Tania / Moyle, Peter Michael

ACS infectious diseases

2020 Volume 6, Issue 7, Page(s) 1770–1782

Abstract: Subunit vaccines composed of protein antigens covalently attached to Toll-like receptor (TLR) agonists elicit superior immune responses compared to mixtures of antigens and TLR agonists. Among different conjugation approaches, enzyme-mediated ligation is ...

Abstract	Subunit vaccines composed of protein antigens covalently attached to Toll-like receptor (TLR) agonists elicit superior immune responses compared to mixtures of antigens and TLR agonists. Among different conjugation approaches, enzyme-mediated ligation is one of the few that provides an opportunity for the generation of homogeneous, molecularly defined products in which protein antigens are maintained with native structures, which is most critical to elicit protective immune responses upon vaccination. Four highly conserved protein antigens from Group A
MeSH term(s)	Adjuvants, Immunologic ; Animals ; Lipoproteins ; Mice ; Streptococcus pyogenes ; Toll-Like Receptor 2 ; Vaccines, Combined
Chemical Substances	Adjuvants, Immunologic ; Lipoproteins ; Toll-Like Receptor 2 ; Vaccines, Combined
Language	English
Publishing date	2020-06-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2373-8227
ISSN (online)	2373-8227
DOI	10.1021/acsinfecdis.0c00047
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Article ; Online: Antibodies and protection against COVID-19

López-Macías, Constantino / Rivera-Hernández, Tania

Revista medica del Instituto Mexicano del Seguro Social

2020 Volume 58, Issue 2, Page(s) 76–77

Abstract: Antibodies are one of the most important components of the immune system against infections. So far, little is known about the contribution of antibodies in the protection against the SARS-CoV-2. Measuring antibody levels in the population will allow to ... ...

Title translation	Los anticuerpos y la protección contra la COVID-19
Abstract	Antibodies are one of the most important components of the immune system against infections. So far, little is known about the contribution of antibodies in the protection against the SARS-CoV-2. Measuring antibody levels in the population will allow to determine who has been infected; this could also be useful to know if people with certain levels of antibodies are already protected against the disease.
MeSH term(s)	Antibodies, Viral ; COVID-19 ; Humans ; Immunoglobulin G ; SARS-CoV-2
Chemical Substances	Antibodies, Viral ; Immunoglobulin G
Language	Spanish
Publishing date	2020-04-13
Publishing country	Mexico
Document type	Journal Article
ZDB-ID	732133-8
ISSN	2448-5667 ; 0443-5117 ; 0484-7849
ISSN (online)	2448-5667
ISSN	0443-5117 ; 0484-7849
DOI	10.24875/RMIMSS.M20000001
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Article ; Online: Humanized Plasminogen Mouse Model to Study Group A Streptococcus Invasive Disease.

Rivera-Hernandez, Tania / Walker, Mark J

Methods in molecular biology (Clifton, N.J.)

2020 Volume 2136, Page(s) 309–316

Abstract: This chapter presents the methodology to carry out infection of humanized plasminogen mice with Group A Streptococcus (GAS). This model of invasive disease has been widely used within the field to study the virulence of different GAS strains, host- ... ...

Abstract	This chapter presents the methodology to carry out infection of humanized plasminogen mice with Group A Streptococcus (GAS). This model of invasive disease has been widely used within the field to study the virulence of different GAS strains, host-pathogen interactions, the importance of particular virulence factors, and preclinical evaluation of novel treatments and vaccines. The model has shown to be highly reproducible and therefore represents an invaluable tool for GAS research.
MeSH term(s)	Animals ; Antigens, Bacterial/metabolism ; Bacterial Outer Membrane Proteins/metabolism ; Bacterial Proteins/metabolism ; Carrier Proteins/metabolism ; Disease Models, Animal ; Host-Pathogen Interactions ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Plasminogen/metabolism ; Protein Binding ; Streptococcal Infections/immunology ; Streptococcus pyogenes/metabolism ; Virulence ; Virulence Factors/metabolism
Chemical Substances	Antigens, Bacterial ; Bacterial Outer Membrane Proteins ; Bacterial Proteins ; Carrier Proteins ; Virulence Factors ; Plasminogen (9001-91-6)
Language	English
Publishing date	2020-05-16
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0467-0_24
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Article ; Online: Challenges in the development of vaccines against COVID-19.

Ontiveros-Padilla, Luis Alberto / Rivera-Hernández, Tania / López-Macías, Constantino

Revista medica del Instituto Mexicano del Seguro Social

2021 Volume 58, Issue Supl 2, Page(s) S116–118

Abstract: In the face of the urgent need for a COVID-19 vaccine, currently more than 90 vaccine candidates are being developed using different strategies, such as inactivated or attenuated SARS-CoV-2 virus, viral vectors expressing antigens of this virus, nucleic ... ...

Title translation	Retos en el desarrollo de vacunas contra COVID-19.
Abstract	In the face of the urgent need for a COVID-19 vaccine, currently more than 90 vaccine candidates are being developed using different strategies, such as inactivated or attenuated SARS-CoV-2 virus, viral vectors expressing antigens of this virus, nucleic acids or purified viral proteins. These vaccines are in preclinical development and at least six of them have already been injected into volunteers in safety clinical trials. However, the characteristics of the protective immune responses are still unknown; therefore, there is not evidence to indicate that these vaccines will induce protection and if this will be long-lasting. The development of SARS-CoV-2 vaccines is vital; nevertheless, it is also important to unveil the characteristics of the protective immune responses to guide the design of a vaccine that generates a long-lasting protection against COVID-19.
Language	Spanish
Publishing date	2021-10-25
Publishing country	Mexico
Document type	Journal Article
ZDB-ID	732133-8
ISSN	2448-5667 ; 0443-5117 ; 0484-7849
ISSN (online)	2448-5667
ISSN	0443-5117 ; 0484-7849
DOI	10.24875/RMIMSS.M20000122
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Article ; Online: Bioinformatic Analysis of B- and T-cell Epitopes from SARS-CoV-2 Structural Proteins and their Potential Cross-reactivity with Emerging Variants and other Human Coronaviruses.

Pacheco-Olvera, Diana Laura / Saint Remy-Hernández, Stephanie / García-Valeriano, María Guadalupe / Rivera-Hernández, Tania / López-Macías, Constantino

Archives of medical research

2022 Volume 53, Issue 7, Page(s) 694–710

Abstract: Background: The mutations in SARS-CoV-2 variants of concern (VOC) facilitate the virus' escape from the neutralizing antibodies induced by vaccines. However, the protection from hospitalization and death is not significantly diminished. Both vaccine ... ...

Abstract	Background: The mutations in SARS-CoV-2 variants of concern (VOC) facilitate the virus' escape from the neutralizing antibodies induced by vaccines. However, the protection from hospitalization and death is not significantly diminished. Both vaccine boosters and infection improve immune responses and provide protection, suggesting that conserved and/or cross-reactive epitopes could be involved. While several important T- and B-cell epitopes have been identified, mainly in the S protein, the M and N proteins and their potential cross-reactive epitopes with other coronaviruses remain largely unexplored. Aims: To identify and map new potential B- and T-cell epitopes within the SARS-CoV-2 S, M and N proteins, as well as cross-reactive epitopes with human coronaviruses. Methods: Different bioinformatics tools were used to: i) Identify new and compile previously-reported B-and T-cell epitopes from SARS-CoV-2 S, M and N proteins; ii) Determine the mutations in S protein from VOC that affect B- and T-cell epitopes, and; iii) Identify cross-reactive epitopes with coronaviruses relevant to human health. Results: New, potential B- and T-cell epitopes from S, M and N proteins as well as cross-reactive epitopes with other coronaviruses were found and mapped within the proteins' structures. Conclusion: Numerous potential B- and T-cell epitopes were found in S, M and N proteins, some of which are conserved between coronaviruses. VOCs present mutations within important epitopes in the S protein; however, a significant number of other epitopes remain unchanged. The epitopes identified here may contribute to augmenting the protective response to SARS-CoV-2 and its variants induced by infection and/or vaccination, and may also be used for the rational design of novel broad-spectrum coronavirus vaccines.
MeSH term(s)	Humans ; Epitopes, T-Lymphocyte/genetics ; Computational Biology ; SARS-CoV-2 ; COVID-19
Chemical Substances	Epitopes, T-Lymphocyte
Language	English
Publishing date	2022-11-03
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1156844-6
ISSN	1873-5487 ; 0188-4409 ; 0188-0128
ISSN (online)	1873-5487
ISSN	0188-4409 ; 0188-0128
DOI	10.1016/j.arcmed.2022.10.007
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Article: Semisynthetic, self-adjuvanting vaccine development: Efficient, site-specific sortase A-mediated conjugation of Toll-like receptor 2 ligand FSL-1 to recombinant protein antigens under native conditions and application to a model group A streptococcal vaccine

Xu, Zhenghui / Rivera-Hernandez, Tania / Chatterjee, Oishee / Walker, Mark J / Moyle, Peter M

Journal of controlled release. 2020 Jan. 10, v. 317

2020

Abstract: Protein antigens are, in general, weakly immunogenic, and therefore require co-delivery with adjuvants to stimulate potent immune responses. The fusion of (poly)peptide antigens to immunostimulatory adjuvants (e.g. Toll-like receptor (TLR) agonists) has ... ...

Abstract	Protein antigens are, in general, weakly immunogenic, and therefore require co-delivery with adjuvants to stimulate potent immune responses. The fusion of (poly)peptide antigens to immunostimulatory adjuvants (e.g. Toll-like receptor (TLR) agonists) has been demonstrated to greatly improve vaccine potency compared to mixtures of antigen and adjuvant. Chemical approaches, to enable the rapid, site-specific and high-yielding linkage of TLR2 ligands to recombinant protein antigens, have been previously optimized. These approaches require the use of denaturing conditions to ensure high reaction yields, which limits their application, as maintenance of native protein folding is necessary to elicit antibodies against conformational epitopes. Here, this work aimed to optimize an alternative method, to ensure the efficient bioconjugation of TLR2 ligands onto folded protein antigens. An enzyme-mediated approach, using Staphylococcus aureus sortase A (or a penta mutant with enhanced efficiency), was optimized for reaction yield and time, as well as enzyme type and amount. This approach enabled the site-specific conjugation of the TLR2-agonist fibroblast-stimulating lipopeptide-1 (FSL-1) onto a model group A Streptococcus (GAS) recombinant polytope antigen under conditions that maintain protein folding, yielding a homogeneous, molecularly-defined product, with ligation yields as high as 90%. Following intramuscular (IM) administration of the ligation product to humanized plasminogen AlbPLG1 mice, high-titer, antigen-specific IgG antibodies were observed, which conferred protection against subcutaneous challenge with GAS strain 5448. In comparison, mixtures of the GAS antigen with aluminum hydroxide or FSL-1 failed to provide protection, with the FSL-1 mixture yielding ~1000-fold lower antigen-specific IgG antibody titers, and the mixture with alum yielding a Th2-biased response compared to the more balanced Th1/Th2 responses observed with the FSL-1 conjugate. Overall, a FSL-1 bioconjugation method for the efficient production of antigen-TLR2 agonist conjugates, which maintain protein folding, was produced, with broad utility for the development of self-adjuvanting vaccines against subunit protein antigens.
Keywords	Staphylococcus aureus ; Streptococcus ; Toll-like receptor 2 ; adjuvants ; agonists ; alum ; aluminum hydroxide ; antibodies ; epitopes ; immune response ; immunoglobulin G ; ligands ; models ; mutants ; peptides ; plasminogen ; protein folding ; recombinant proteins ; sortase A ; vaccine development ; vaccines
Language	English
Dates of publication	2020-0110
Size	p. 96-108.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2019.11.018
Database	NAL-Catalogue (AGRICOLA)

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Article: Efficacy of Alum-Adjuvanted Peptide and Carbohydrate Conjugate Vaccine Candidates against Group A

Rivera-Hernandez, Tania / Carnathan, Diane G / Richter, Johanna / Marchant, Patrick / Cork, Amanda J / Elangovan, Gayathiri / Henningham, Anna / Cole, Jason N / Choudhury, Biswa / Moyle, Peter M / Toth, Istvan / Batzloff, Michael R / Good, Michael F / Agarwal, Paresh / Kapoor, Neeraj / Nizet, Victor / Silvestri, Guido / Walker, Mark J

Vaccines

2024 Volume 12, Issue 4

Abstract: Vaccine development against group ... ...

Abstract	Vaccine development against group A
Language	English
Publishing date	2024-04-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12040382
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Article ; Online: Author Correction: Pathogenesis, epidemiology and control of Group A Streptococcus infection.

Brouwer, Stephan / Rivera-Hernandez, Tania / Curren, Bodie F / Harbison-Price, Nichaela / De Oliveira, David M P / Jespersen, Magnus G / Davies, Mark R / Walker, Mark J

Nature reviews. Microbiology

2023 Volume 21, Issue 9, Page(s) 619

Language	English
Publishing date	2023-07-03
Publishing country	England
Document type	Published Erratum
ZDB-ID	2139054-X
ISSN	1740-1534 ; 1740-1526
ISSN (online)	1740-1534
ISSN	1740-1526
DOI	10.1038/s41579-023-00939-6
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Article ; Online: Pathogenesis, epidemiology and control of Group A Streptococcus infection.

Brouwer, Stephan / Rivera-Hernandez, Tania / Curren, Bodie F / Harbison-Price, Nichaela / De Oliveira, David M P / Jespersen, Magnus G / Davies, Mark R / Walker, Mark J

Nature reviews. Microbiology

2023 Volume 21, Issue 7, Page(s) 431–447

Abstract: Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. ... ...

Abstract	Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. GAS deploys a range of virulence determinants to allow colonization, dissemination within the host and transmission, disrupting both innate and adaptive immune responses to infection. Fluctuating global GAS epidemiology is characterized by the emergence of new GAS clones, often associated with the acquisition of new virulence or antimicrobial determinants that are better adapted to the infection niche or averting host immunity. The recent identification of clinical GAS isolates with reduced penicillin sensitivity and increasing macrolide resistance threatens both frontline and penicillin-adjunctive antibiotic treatment. The World Health Organization (WHO) has developed a GAS research and technology road map and has outlined preferred vaccine characteristics, stimulating renewed interest in the development of safe and effective GAS vaccines.
MeSH term(s)	Humans ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Macrolides/pharmacology ; Macrolides/therapeutic use ; Drug Resistance, Bacterial ; Streptococcal Infections/drug therapy ; Streptococcal Infections/epidemiology ; Streptococcal Infections/prevention & control ; Streptococcus pyogenes/genetics ; Penicillins/therapeutic use
Chemical Substances	Anti-Bacterial Agents ; Macrolides ; Penicillins
Language	English
Publishing date	2023-03-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2139054-X
ISSN	1740-1534 ; 1740-1526
ISSN (online)	1740-1534
ISSN	1740-1526
DOI	10.1038/s41579-023-00865-7
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Article ; Online: Immunogenicity Assessment of Cell Wall Carbohydrates of Group A

Khatun, Farjana / Dai, Charles C / Rivera-Hernandez, Tania / Hussein, Waleed M / Khalil, Zeinab G / Capon, Robert J / Toth, Istvan / Stephenson, Rachel J

ACS infectious diseases

2021 Volume 7, Issue 2, Page(s) 390–405

Abstract: Identifying the immunogenic moieties and their precise structure of carbohydrates plays an important role for developing effective carbohydrate-based subunit vaccines. This study assessed the structure-immunogenicity relationship of carbohydrate moieties ...

Abstract	Identifying the immunogenic moieties and their precise structure of carbohydrates plays an important role for developing effective carbohydrate-based subunit vaccines. This study assessed the structure-immunogenicity relationship of carbohydrate moieties of a single repeating unit of group A carbohydrate (GAC) present on the cell wall of group A
MeSH term(s)	Adjuvants, Immunologic ; Animals ; Carbohydrates ; Cell Wall ; Lipopeptides ; Mice ; Streptococcus pyogenes
Chemical Substances	Adjuvants, Immunologic ; Carbohydrates ; Lipopeptides
Language	English
Publishing date	2021-02-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2373-8227
ISSN (online)	2373-8227
DOI	10.1021/acsinfecdis.0c00722
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