Subclass distribution of natural salivary IgA antibodies against pneumococcal capsular polysaccharide of type 14 and pneumococcal surface adhesin A (PsaA) in children

Simell, Birgit; Kilpi, Terhi; Käyhty, Helena

doi:10.1111/j.1365-2249.2006.03009.x

Cited by 18 publications

(5 citation statements)

References 35 publications

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“…While IgA1 responds to protein and polysaccharide antigens, IgA2 seems to specialize in polysaccharide antigens. 86,87 Despite its lack of FcgR interaction, IgA possesses significant effector functions that occur through binding to FcaRI on various leukocytes. While binding to macrophages and neutrophils elicits phagocytosis, neutrophils and eosinophils release cytotoxic granules in an ADCC mechanism similar to that of IgG-ligated NK cells.…”

Section: Immunoglobulin Amentioning

confidence: 99%

Considerations for the Design of Antibody-Based Therapeutics

Goulet

Atkins

2020

Journal of Pharmaceutical Sciences

201

154

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Keywords: antibody(s) antibody drug(s) antibody drug conjugate(s) (ADC) physicochemical properties pharmacokinetics monoclonal antibody(s) immunotherapy IgG antibody(s) drug design developability a b s t r a c t Antibody-based proteins have become an important class of biologic therapeutics, due in large part to the stability, specificity, and adaptability of the antibody framework. Indeed, antibodies not only have the inherent ability to bind both antigens and endogenous immune receptors but also have proven extremely amenable to protein engineering. Thus, several derivatives of the monoclonal antibody format, including bispecific antibodies, antibody-drug conjugates, and antibody fragments, have demonstrated efficacy for treating human disease, particularly in the fields of immunology and oncology. Reviewed here are considerations for the design of antibody-based therapeutics, including immunological context, therapeutic mechanisms, and engineering strategies. First, characteristics of antibodies are introduced, with emphasis on structural domains, functionally important receptors, isotypic and allotypic differences, and modifications such as glycosylation. Then, aspects of therapeutic antibody design are discussed, including identification of antigen-specific variable regions, choice of expression system, use of multispecific formats, and design of antibody derivatives based on fragmentation, oligomerization, or conjugation to other functional moieties. Finally, strategies to enhance antibody function through protein engineering are reviewed while highlighting the impact of fundamental biophysical properties on protein developability.

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Section: Immunoglobulin Amentioning

confidence: 99%

Considerations for the Design of Antibody-Based Therapeutics

Goulet

Atkins

2020

Journal of Pharmaceutical Sciences

201

154

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“…Further investigation as to whether loss of diversity in the B cell repertoire correlated with poor vaccine responses against influenza and pneumonia indicated that it may be a contributory factor, but that other factors were likely also involved (Ademokun et al, 2011 ). These two vaccines generate different responses; influenza is believed to mainly induce IgG1/IgG3/IgA1 T-dependent responses (Brown et al, 1985 ; Hocart et al, 1990 ; Powers, 1994 ), while pneumococcal responses are thought to be T-independent and can lead to significant elevation of IgA2/IgG2 antibodies in the serum and mucosa (Lue et al, 1988 ; Carson et al, 1995 ; Sanal et al, 1999 ; Simell et al, 2006 ; Benckert et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Age-Related Changes in Human Peripheral Blood IGH Repertoire Following Vaccination

Wu¹,

Kipling²,

Dunn-Walters³

2012

Front. Immun.

105

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Immune protection against pulmonary infections, such as seasonal flu and invasive pneumonia, is severely attenuated with age, and vaccination regimes for the elderly people often fail to elicit effective immune response. We have previously shown that influenza and pneumococcal vaccine responses in the older population are significantly impaired in terms of serum antibody production, and have shown repertoire differences by CDR-H3 spectratype analysis. Here we report a detailed analysis of the B cell repertoire in response to vaccine, including a breakdown of sequences by class and subclass. Clustering analysis of high-throughput sequencing data enables us to visualize the response in terms of expansions of clonotypes, changes in CDR-H3 characteristics, and somatic hypermutation as well as identifying the commonly used IGH genes. We have highlighted a number of significant age-related changes in the B cell repertoire. Interestingly, in light of the fact that IgG is the most prevalent serum antibody and the most widely used as a correlate of protection, the most striking age-related differences are in the IgA response, with defects also seen in the IgM repertoire. In addition there is a skewing toward IgG2 in the IgG sequences of the older samples at all time points. This analysis illustrates the importance of antibody classes other than IgG and has highlighted a number of areas for future consideration in vaccine studies of the elderly.

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“…The innate B cell response is based on the specificity of the antibody (germline-encoded antibody specificities), the faster kinetics of antibody generation by some B cell subsets and memory in the form of a preformed, perhaps somewhat static repertoire. Subsets of B cells (B-1 and marginal zone) based on expression of a skewed antibody specificity are part of the innate immune B cell system, and in some cases were clearly shown to produce highly protective natural antibodies (IgA) against Streptococcus pneumonia (211). Using transgenic mice Haas and co-workers demonstrated that B1a B cells are necessary for natural antibody that reduced the susceptibility to infection while B1b cells produced protective anti-pneumococcal polysaccharide antibody (93).…”

Section: Receptor Specificity Of Innate and Adaptive B Cellsmentioning

confidence: 99%

The ABCs (Antibody, B Cells, and Carbohydrate Epitopes) of Cholera Immunity: Considerations for an Improved Vaccine

Provenzano

Kòváč

Wade

2006

Microbiology and Immunology

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A Gram-negative bacterium, V. cholerae, causes cholera, the paradigm of water-born infections. Cholera is a highly contagious diarrheal disease (34,199). Diarrhea, which may range from moderate to severe, appears within 1-5 days of ingestion of contaminated food or water. Massive fluid loss and electrolyte imbalance can lead to high mortality if fluid replacement is not provided. Many cholera survivors are immune to a second infection showing that immunity can be acquired (140). Since 1854, when Dr. John Snow demonstrated the cholera contagion at the Broad Street pump in London, and later when Robert Koch (1884) isolated the cholera bacterium in pure culture, biomedical investigators have relentlessly pursued the understanding of V. cholerae pathogenesis in an attempt to prevent future cholera epidemics. As a result, the biology of both cholera and of V. cholerae have become increasingly clear. We know of V. cholerae's ability to sense the environment and respond to different metabolic needs either in estuaries or in the human host (258). We know of El Nino's climatic influence on V. cholerae in Latin America and of the seasonal influence on cholera in endemic areas (126). The potential for V. cholerae bacterial phages to limit (by lysis) the aquatic pool of V. cholerae has been postulated to play a role in endemic cholera (69). Received April 26, 2006Abstract: Cholera, a diarrheal disease, is known for explosive epidemics that can quickly kill thousands. Endemic cholera is a seasonal torment that also has a significant mortality. Not all nations with extensive rural communities can achieve the required infrastructure or behavioral changes to prevent epidemic or endemic cholera. For some communities, a single-dose cholera vaccine that protects those at risk is the most efficacious means to reduce morbidity and mortality. It is clear that our understanding of what a protective cholera immune response is has not progressed at the rate our understanding of the pathogenesis and molecular biology of cholera infection has. This review addresses V. cholerae lipopolysaccharide (LPS)-based immunogens because LPS is the only immunogen proven to induce protective antibody in humans. We discuss the role of anti-LPS antibodies in protection from cholera, the importance and the potential role of B cell subsets in protection that is based on their anatomical location and the intrinsic antigen-receptor specificity of various subsets is introduced.

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Subclass distribution of natural salivary IgA antibodies against pneumococcal capsular polysaccharide of type 14 and pneumococcal surface adhesin A (PsaA) in children

Cited by 18 publications

References 35 publications

Considerations for the Design of Antibody-Based Therapeutics

Considerations for the Design of Antibody-Based Therapeutics

Age-Related Changes in Human Peripheral Blood IGH Repertoire Following Vaccination

The ABCs (Antibody, B Cells, and Carbohydrate Epitopes) of Cholera Immunity: Considerations for an Improved Vaccine

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