Carbohydrates as T-cell antigens with implications in health and disease

Sun, Lina; Middleton, Dustin R.; Wantuch, Paeton L; Ozdilek, Ahmet; Avci, Fikri Y.

doi:10.1093/glycob/cww062

Cited by 70 publications

(50 citation statements)

References 142 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Active immunization with carbohydrate antigens elicits glycan-specific protective immune responses. Poorly immunogenic carbohydrate antigens and ill-defined conjugation render the production of carbohydratebased vaccines challenging (27). Licensed polysaccharide-based 7-, 10-, and 13-valent pneumococcal conjugate vaccines are effective in significantly reducing the burden of IPD-related mortality and morbidity (8).…”

Section: Discussionmentioning

confidence: 99%

Improving vaccines against Streptococcus pneumoniae using synthetic glycans

Kapłonek

Khan

Reppe

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Streptococcus pneumoniae remains a deadly disease in small children and the elderly even though conjugate and polysaccharide vaccines based on isolated capsular polysaccharides (CPS) are successful. The most common serotypes that cause infection are used in vaccines around the world, but differences in geographic and demographic serotype distribution compromises protection by leading vaccines. The medicinal chemistry approach to glycoconjugate vaccine development has helped to improve the stability and immunogenicity of synthetic vaccine candidates for several serotypes leading to the induction of higher levels of specific protective antibodies. Here, we show that marketed CPS-based glycoconjugate vaccines can be improved by adding synthetic glycoconjugates representing serotypes that are not covered by existing vaccines. Combination (coformulation) of synthetic glycoconjugates with the licensed vaccines Prevnar13 (13-valent) and Synflorix (10-valent) yields improved 15-and 13-valent conjugate vaccines, respectively, in rabbits. A pentavalent semisynthetic glycoconjugate vaccine containing five serotype antigens (sPCV5) elicits antibodies with strong in vitro opsonophagocytic activity. This study illustrates that synthetic oligosaccharides can be used in coformulation with both isolated polysaccharide glycoconjugates to expand protection from existing vaccines and each other to produce precisely defined multivalent conjugated vaccines. synthetic glycans | vaccine | Streptococcus pneumoniae C apsular polysaccharides (CPS) surround many deadly human pathogens. Polysaccharide-conjugated vaccines, based on isolated CPS antigens attached to carrier proteins, protect young children and the elderly from deadly bacterial pathogens including Haemophilus influenzae type b (Hib), Neisseria meningitides, and the encapsulated gram-positive bacterium Streptococcus pneumoniae. S. pneumoniae is the leading cause of life-endangering diseases such as pneumonia, septicemia, and meningitis (1), and a major cause of death in children under five in developing countries (2-4). More than 90 S. pneumoniae serotypes can be distinguished based on their CPS (5, 6). Currently available CPS-based pneumococcal vaccines contain the serotypes most frequently associated with invasive pneumococcal diseases (IPDs). Although the licensed 23-valent polysaccharide vaccine (Pneumovax 23) is not effective in younger children (3, 7), the conjugate vaccines Prevnar13 and Synflorix cover 13 and 10 serotypes, respectively, and are highly successful in all age groups (8). Nevertheless, serotype replacement due to vaccination and regional differences in dominant serotypes necessitate the expansion of existing vaccines to include additional serotypes. An additional weak point is that some serotype antigens, such as ST5 and ST1, that are present in existing vaccines undergo undesired chemical modification during production (9, 10); others have limited immunogenicity and lead to protective levels well below those required for herd immunity, such as SP3 (6).The p...

show abstract

Section: Discussionmentioning

confidence: 99%

Improving vaccines against Streptococcus pneumoniae using synthetic glycans

Kapłonek

Khan

Reppe

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…5 The majority of these factors can be attributed to the short-lived IgM antibodies elicited from the T-cell independent response, no affinity maturation, and lack of IgG class switching of antibodies. 17 The solution for these issues came with the introduction of the T cell dependent conjugate vaccines in the 2000s. …”

Section: Characteristics Of the Bacteriummentioning

confidence: 99%

Current status and future directions of invasive pneumococcal diseases and prophylactic approaches to control them

Wantuch

Avci

2018

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Streptococcus pneumoniae is a major human bacterial pathogen responsible for millions of deaths each year and significantly more illnesses worldwide. With over 90 different serotypes, providing effective vaccine programs has been a continuing challenge. Since 1983, the world has been introduced to four different pneumococcal vaccines (PPSV23, PCV7, PCV10, and PCV13) each with their own complications and successes. Since vaccination programs began, a decrease in the overall rate of pneumococcal pneumonia and associated diseases has been observed, notably in higher risk populations. However, with a decrease in incidence of vaccine type pneumococcal serotypes, increases in non-vaccine serotypes of the bacteria have been observed along with serotype switching. Additionally, a rise in antibiotic resistant strains of S. pneumoniae is noted. Here we discuss both the positive and negative clinical manifestations of pneumonia vaccine programs and discuss the challenges in pneumococcal vaccine design.

show abstract

“…Another element that may be involved in epitope selection of HA is sites of N-linked glycosylation. Although it is known that some glycopeptides can elicit CD4 T cells (reviewed in [71,72]), it is possible that the sites of complex or very large N-linked glycosylation may shield segments of HA from proteolysis, as has been observed for the endosomal proteins LAMP-1 and LAMP-2 [73] and synthetic peptides [74]. Alternatively, the N-linked carbohydrate may obstruct CD4 T cell receptor recognition.…”

Section: Discussionmentioning

confidence: 99%

Peptide Epitope Hot Spots of CD4 T Cell Recognition Within Influenza Hemagglutinin During the Primary Response to Infection

et al. 2019

View full text Add to dashboard Cite

Antibodies specific for the hemagglutinin (HA) protein of influenza virus are critical for protective immunity to infection. Our studies show that CD4 T cells specific for epitopes derived from HA are the most effective in providing help for the HA-specific B cell responses to infection and vaccination. In this study, we asked whether HA epitopes recognized by CD4 T cells in the primary response to infection are equally distributed across the HA protein or if certain segments are enriched in CD4 T cell epitopes. Mice that collectively expressed eight alternative MHC (Major Histocompatibility Complex) class II molecules, that would each have different peptide binding specificities, were infected with an H1N1 influenza virus. CD4 T cell peptide epitope specificities were identified by cytokine EliSpots. These studies revealed that the HA-specific CD4 T cell epitopes cluster in two distinct regions of HA and that some segments of HA are completely devoid of CD4 T cell epitopes. When located on the HA structure, it appears that the regions that most poorly recruit CD4 T cells are sequestered within the interior of the HA trimer, perhaps inaccessible to the proteolytic machinery inside the endosomal compartments of antigen presenting cells.

show abstract

Carbohydrates as T-cell antigens with implications in health and disease

Cited by 70 publications

References 142 publications

Improving vaccines against Streptococcus pneumoniae using synthetic glycans

Improving vaccines against Streptococcus pneumoniae using synthetic glycans

Current status and future directions of invasive pneumococcal diseases and prophylactic approaches to control them

Peptide Epitope Hot Spots of CD4 T Cell Recognition Within Influenza Hemagglutinin During the Primary Response to Infection

Contact Info

Product

Resources

About