Study of Avidity of Antigen-Specific Antibody as a Means of Understanding Development of Long-Term Immunological Memory after Vibrio cholerae O1 Infection

Alam, Mohammad Murshid; Arifuzzaman, Mohammad; Ahmad, Shaikh Meshbahuddin; Hosen, Ismail; Rahman, Mohammad Arif; Rashu, Rasheduzzaman; Sheikh, Alaullah; Ryan, Edward T.; Calderwood, Stephen B.; Qadri, Firdausi

doi:10.1128/cvi.00521-12

Cited by 29 publications

(44 citation statements)

References 41 publications

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“…Antibody avidity, which examines the functional affinity of antibodyantigen interactions, has been used as marker of B cell maturation and a surrogate of protective immunity to a number of important pathogens. Importantly, antibody avidity has been shown to correlate with the presence of antigen-specific memory B cells following Vibrio cholerae infection (27), potentially permitting efficient measurement of responses that might predict protection against a number of important diarrheal pathogens. Interestingly, the se- rum IgG antibody avidity in the intradermally vaccinated mice was considerably lower than that in the mice vaccinated orally with EtpA (P ϭ 0.002) (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Immunogenicity and Protective Efficacy against Enterotoxigenic Escherichia coli Colonization following Intradermal, Sublingual, or Oral Vaccination with EtpA Adhesin

Luo

Vickers

Fleckenstein

2016

Clin Vaccine Immunol

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c Enterotoxigenic Escherichia coli (ETEC) strains are a common cause of diarrhea. Extraordinary antigenic diversity has prompted a search for conserved antigens to complement canonical approaches to ETEC vaccine development. EtpA, an immunogenic extracellular ETEC adhesin relatively conserved in the ETEC pathovar, has previously been shown to be a protective antigen following intranasal immunization. These studies were undertaken to explore alternative routes of EtpA vaccination that would permit use of a double mutant (R192G L211A) heat-labile toxin (dmLT) adjuvant. Here, oral vaccination with EtpA adjuvanted with dmLT afforded significant protection against small intestinal colonization, and the degree of protection correlated with fecal IgG, IgA, or total fecal antibody responses to EtpA. Sublingual vaccination yielded compartmentalized mucosal immune responses with significant increases in anti-EtpA fecal IgG and IgA, and mice vaccinated via this route were also protected against colonization. In contrast, while intradermal (i.d.) vaccination achieved high levels of both serum and fecal antibodies against both EtpA and dmLT, mice vaccinated via the i.d. route were not protected against subsequent colonization and the avidity of serum IgG and IgA EtpA-specific antibodies was significantly lower after i.d. immunization compared to other routes. Finally, we demonstrate that antiserum from vaccinated mice significantly impairs binding of LT to cognate GM1 receptors and shows near complete neutralization of toxin delivery by ETEC in vitro. Collectively, these data provide further evidence that EtpA could complement future vaccine strategies but also suggest that additional effort will be required to optimize its use as a protective immunogen. Enterotoxigenic Escherichia coli (ETEC) strains are among the most common causes of diarrheal illness in developing countries, where young children are most susceptible (1, 2). In addition, these pathogens are also a common cause of diarrhea in immunologically naive travelers (3) who venture to areas of endemicity where sanitation and clean water remain limited.Given the significant impact of ETEC on global health, a vaccine to prevent these infections is a significant priority (4). However, despite decades of investigative efforts following the discovery of toxin-producing E. coli in patients with clinical illnesses indistinguishable from cholera (5), a vaccine that affords broadbased protection has yet to be developed.All of the ETEC-specific virulence genes described to date are encoded on plasmids. These include the heat-labile and/or heatstable enterotoxins that define this pathovar and the colonization factors (CFs). Most vaccines to date have primarily targeted these colonization factors, which include a broad array of fimbrial as well as afimbrial surface antigens thought to be essential for intestinal colonization and/or heat-labile toxin.Unfortunately, the heterogeneity of CF antigenic structures presents a challenge to development of a broadly protective vaccine. ...

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Section: Resultsmentioning

confidence: 99%

“…Avidity indexes for EtpA-specific serum IgG and IgA antibodies were determined as previously described (27). Briefly, microtiter wells were coated with EtpA as described above.…”

Section: Methodsmentioning

confidence: 99%

Immunogenicity and Protective Efficacy against Enterotoxigenic Escherichia coli Colonization following Intradermal, Sublingual, or Oral Vaccination with EtpA Adhesin

Luo

Vickers

Fleckenstein

2016

Clin Vaccine Immunol

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“…The existence of antibodies that have a high avidity for their antigen proved that recombinant HBsAg can induce the humoral memory response (Joseph et al, 2001;Alam et al, 2013). However, the memory response to HBsAg was more difficult to evaluate.…”

Section: R E T R a C T I O Nmentioning

confidence: 99%

Immune memory responses to HBV vaccine 13-18 years after primary vaccination

Hou¹,

Li²,

Wei³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to evaluate the immune memory response 13-18 years after an hepatitis B virus (HBV) vaccine by performing a specific in vitro stimulation experiment. Thirty healthy volunteers who had been inoculated 13-18 years ago with the HBV vaccine were collected from the physical examination center. Peripheral blood mononuclear cells were stimulated with 50 ng/mL recombinant HBsAg. An ELISA kit was used for the detection of antibodies that were produced by these cells in vitro. It was found that even 13-18 years after inoculation with the HBV vaccine, an anamnestic antibody response still existed, and was not correlated with the serum antibody levels (r = -0.177, P = 0.377).In conclusion, our data showed that the individuals after inoculation, including those with anti-HBs <10 IU/L as well as those individuals in whom the antibody was not detected, retained immune memory, which may be the main role of memory B cells.

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“…We showed previously, in adults, that the avidity of antibodies against both cholera toxin B subunit (CTB) and LPS increases following cholera infection or cholera vaccination and correlates with the levels of memory B cells against the respective antigens; the durability of high-avidity antibodies is longer in patients than in vaccinees (15).…”

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confidence: 99%

Antibody Avidity in Humoral Immune Responses in Bangladeshi Children and Adults following Administration of an Oral Killed Cholera Vaccine

Alam

Leung

Akhtar

et al. 2013

Clin. Vaccine Immunol.

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e Antibody avidity for antigens following disease or vaccination increases with affinity maturation and somatic hypermutation. In this study, we followed children and adults in Bangladesh for 1 year following oral cholera vaccination and measured the avidity of antibodies to the T cell-dependent antigen cholera toxin B subunit (CTB) and the T cell-independent antigen lipopolysaccharide (LPS) in comparison with responses in other immunological measurements. Children produced CTB-specific IgG and IgA antibodies of high avidity following vaccination, which persisted for several months; the magnitudes of responses were comparable to those seen in adult vaccinees. The avidity of LPS-specific IgG and IgA antibodies in vaccinees increased significantly shortly after the second dose of vaccine but waned rapidly to baseline levels thereafter. CTB-specific memory B cells were present for only a short time following vaccination, and we did not find significant memory B cell responses to LPS in any age group. For older children, there was a significant correlation between CTB-specific memory T cell responses after the second dose of vaccine and CTB-specific IgG antibody avidity indices over the subsequent year. These findings suggest that vaccination induces a longer-lasting increase in the avidity of antibodies to a T cell-dependent antigen than is measured by a memory B cell response to that antigen and that early memory T cell responses correlate well with the subsequent development of higher-avidity antibodies.

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Study of Avidity of Antigen-Specific Antibody as a Means of Understanding Development of Long-Term Immunological Memory after Vibrio cholerae O1 Infection

Cited by 29 publications

References 41 publications

Immunogenicity and Protective Efficacy against Enterotoxigenic Escherichia coli Colonization following Intradermal, Sublingual, or Oral Vaccination with EtpA Adhesin

Immunogenicity and Protective Efficacy against Enterotoxigenic Escherichia coli Colonization following Intradermal, Sublingual, or Oral Vaccination with EtpA Adhesin

Immune memory responses to HBV vaccine 13-18 years after primary vaccination

Antibody Avidity in Humoral Immune Responses in Bangladeshi Children and Adults following Administration of an Oral Killed Cholera Vaccine

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