Avidity and Subclasses of IgG after Immunization of Infants with an 11‐Valent Pneumococcal Conjugate Vaccine with or without Aluminum Adjuvant

Wuorimaa, Tomi; Dagan, Ron; Väkeväinen, Merja; Bailleux, Fabrice; Haikala, Raili; Yaich, Mansour; Eskola, Juhani; Käyhty, Helena

doi:10.1086/323648

Cited by 74 publications

(48 citation statements)

References 14 publications

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“…3D). An increase of overall avidity through the use of aluminum salts as adjuvants has previously been described in immunization studies in mice and humans (54,55,65). Second, through the use of a mutant DIII with modifications at the so-called lateral ridge epitope originally described in the West Nile virus system (36), we found that the ϪAlu group had a higher proportion of antibodies against this specific epitope than the ϩAlu group.…”

Section: Discussionsupporting

confidence: 63%

Aluminum Hydroxide Influences Not Only the Extent but Also the Fine Specificity and Functional Activity of Antibody Responses to Tick-Borne Encephalitis Virus in Mice

Zlatkovic

Tsouchnikas

Jarmer

et al. 2013

J Virol

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Aluminum hydroxide is the most widely used adjuvant in human vaccines and serves as a potent enhancer of antibody production. Its stimulatory effect strongly depends on the adsorption of the antigen to the adjuvant, which may influence antigen presentation and, as a consequence, the fine specificity of antibody responses. Such variations can have functional consequences and can modulate the effectiveness of humoral immunity. Therefore, we investigated the influence of aluminum hydroxide on the fine specificity of antibody responses in a model study in mice using an inactivated purified virus particle, the flavivirus tickborne encephalitis (TBE) virus, as an immunogen. To dissect and quantify the specificities of polyclonal antibodies in postimmunization sera, we established a platform of immunoassays using recombinant forms of the major target of neutralizing antibodies (protein E) as well as individual domains of E (DIII and the combination of DI and DII [DI؉DII]). Our analyses revealed a higher proportion of neutralizing than virion binding (as detected by enzyme-linked immunosorbent assay) antibodies after immunization with aluminum hydroxide. Furthermore, the induction of antibodies to DIII, a known target of potently neutralizing antibodies, as well as their contributions to virus neutralization were significantly greater in mice immunized with adjuvant and correlated with a higher avidity of these antibodies. Thus, our data provide evidence that aluminum hydroxide can lead to functionally relevant modulations of antibody fine specificities in addition to its known overall immune enhancement effect.

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Section: Discussionsupporting

confidence: 63%

Aluminum Hydroxide Influences Not Only the Extent but Also the Fine Specificity and Functional Activity of Antibody Responses to Tick-Borne Encephalitis Virus in Mice

Zlatkovic

Tsouchnikas

Jarmer

et al. 2013

J Virol

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“…This alteration in avidity is also described in several infections such as Rubella, Toxoplasmosis, and hepatitis B (5, 13). Avidity is established through the affi nity maturation of antibodies to immune response and it is thought that higher avidity goes together with the potent functional activities of antibodies (14,15). The increase in antibody avidity stabilizes immune complexes (antigen-antibody complexes) against protein denaturing agents present in the environment and these agents can dissociate low affi nity antibodies from immune complexes readily.…”

Section: Discussionmentioning

confidence: 99%

Determination of serological profiles and avidity of specific antibodies in the sera of patients with potential Epstein-Barr virus (EBV) infection

Akpolat¹,

Gedik²,

Nergiz³

et al. 2013

BLL

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Abstract:Background: Epstein-Barr Virus, frequently referred to as EBV, is a member of the herpesvirus family and one of the most common human viruses. The virus occurs worldwide, and most people become infected with EBV sometime during their lives. Objectives: The purpose of this study was to investigate the serological profi les of specifi c antibodies among the sera of suspected EBV infection patients along with VCA-IgG avidity. Methods: A total of 522 patient's sera were sent to The Clinical Microbiology Laboratory for EBV specifi c antibody detection and were studied by IFA method during a two year period. The serum samples were tested for EBV specifi c VCA IgG, VCA IgM, EA, EBNA antibodies and VCA IgG aviditity. Results: Among 33 patients those who had low avidity for VCA IgG, 27 (81.8 %) of them had a serologic profi le as follows; positive VCA IgG, negative VCA IgM, negative EA and negative EBNA. Conclusion: While this profi le is considered as a primary infection, the frequency of the coexistence of VCA IgG low avidity with this profi le is interepreted that avidity may lead to detect primary infection (Tab. 2, Ref. 25 Abbreviations: IFA -indirect fl uorescent antibody, EBV -Epstein-Barr virus, EA -early antigen,VCA -viral capsid antigen, EBNA -epstein-barr nuclear antigen.Epstein-Barr virus, commonly referred to as EBV, is a human specifi c member of the herpesvirus family and is a B-cell lymphotropic virus. An EBV infection occurs by close contact with EBV presented in oral secretions. The virus initially wells in the oropharyngeal epithelial cells and causes persistent infections. Seroepidemiologic studies indicate that EBV infections are common in all communities and occur worldwide, and most people become infected with EBV sometime during their lives. In Europe including Turkey, as many as 70-80 % of adolescents and 80-90 % of adults are reported to be seropositive for EBV (1).The course of EBV infection can vary with regard to the age and health status of the person. In young children host-virus infection can take place with no apparent symptoms. By contrast, in 30-50 % of the adult patients EBV infection can cause diffuse lymphadenopathy, hepatomegaly, splenomegaly, and tonsillitis. In some cases exanthematous reactions triggered by EBV can be mistaken with an eruption of rubella (2). Moreover, EBV infection is shown to be associated with lymphoproliferative disorders in patients who are suffering from immunodefi ciency, Burkitt lymphoma, and nasopharyngeal carcinoma (3,4). Infectious mononucleosis is also caused by infection of B cells by EBV and is generally diagnosed by serological methods. EBV serology is utilized to help distinguish EBV reactivation infections from primary EBV infections and to demonstrate acute EBV infections. During this process, it is critically important to perform the tests at the same time for the presence of EBV-VCA IgM, EBV-VCAIgG, anti-EBV-EA, anti EBV-EBNA and VCA IgG avidity (2).The spectrum of antibody assays comprises unspecifi c tests, such as the long-known te...

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“…Each serum pool was collected from post-booster sera of 5 to 11 different children and contained low, medium, or high concentrations of serotype-specific antibodies. The mean capsule type-specific antibody concentrations of the serum pools were calculated based on concentrations of the individual sera previously measured with EIA (52).…”

Section: Methodsmentioning

confidence: 99%

The Capsular Serotype ofStreptococcus pneumoniaeIs More Important than the Genetic Background for Resistance to Complement

et al. 2010

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The polysaccharide capsule of Streptococcus pneumoniae inhibits phagocytic killing by innate immune mechanisms. Certain serotypes are associated with invasive disease while others with a nasopharyngeal carriage. The invasiveness of serotypes may partly be explained by ability to resist deposition of complement (C3) on the bacterial surface and consequent opsonophagocytic killing. In our previous studies, we observed that clinical isolates of serotypes 1 and 5, which are rarely detected in asymptomatic carriage, were resistant to complement deposition and opsonophagocytosis, whereas serotypes 6B and 23F, both common in carriage, were more sensitive to deposition of C3 and opsonophagocytic killing. However, presence of significant variation in C3 deposition between isolates of the same serotype indicated that factors other than the capsule also affect complement resistance. To distinguish the relative effect of the capsular serotype and other virulence factors on C3 deposition, we compared capsule-switched mutants prepared in genetic backgrounds of pneumococcal strains TIGR4, 603, and 618. Clinical isolates which had the same multilocus sequence type but expressed different serotypes were also compared. We found that the serotype had a significant impact on complement resistance and that the more resistant the strain was to complement, the higher was the concentration of polysaccharide-specific antibodies required for opsonophagocytic killing. Comparison of strains expressing the same capsular polysaccharides in the different genetic backgrounds and various capsular mutants of the same strain suggests that while the genotype affects complement resistance, the serotype is the most important determinant. Differences between serotypes were more significant than the differences between strains.

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Avidity and Subclasses of IgG after Immunization of Infants with an 11‐Valent Pneumococcal Conjugate Vaccine with or without Aluminum Adjuvant

Cited by 74 publications

References 14 publications

Aluminum Hydroxide Influences Not Only the Extent but Also the Fine Specificity and Functional Activity of Antibody Responses to Tick-Borne Encephalitis Virus in Mice

Aluminum Hydroxide Influences Not Only the Extent but Also the Fine Specificity and Functional Activity of Antibody Responses to Tick-Borne Encephalitis Virus in Mice

Determination of serological profiles and avidity of specific antibodies in the sera of patients with potential Epstein-Barr virus (EBV) infection

The Capsular Serotype ofStreptococcus pneumoniaeIs More Important than the Genetic Background for Resistance to Complement

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