Formulation, stability and immunogenicity of a trivalent pneumococcal protein vaccine formulated with aluminum salt adjuvants

Ljutic, Belma; Ochs, Martina M.; Messham, Benjamin; Ming, Marin; Dookie, Annie; Harper, Kevin; Ausar, Salvador F.

doi:10.1016/j.vaccine.2012.02.038

Cited by 36 publications

(30 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, in our experiments the antigen was completely adsorbed immediately after mixing with the adjuvant (data not shown). Previous studies have revealed that the interaction with aluminum hydroxide, which strongly depends on the properties of the antigen, buffer composition, pH, and physicochemical properties of the aluminum preparation used, can affect the structure of protein immunogens (15)(16)(17)(18). Flavivirus particles are probably especially prone to adsorption-related structural effects, since the organization of their E proteins in the viral membrane is subject to dynamic changes (29,30,67), can be fixed in different configurations (e.g., by the interaction with specific antibodies [67]), and can undergo extensive temperaturedependent rearrangements (29,30,67).…”

Section: Discussionmentioning

confidence: 99%

“…In the case of protein antigens, this interaction can lead to changes in the secondary or tertiary structure and can affect protein stability (15)(16)(17)(18). Since adsorption-induced effects on protein structure can potentially modulate the fine specificities and, consequently, the functional activities of antibodies elicited by immunization, such changes can affect the effectiveness of vaccination.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…The samples were then centrifuged for 5 min at 4000 £ g. The supernatants were collected and the E6020 concentration was measured by reversed-phase high performance liquid chromatography (RP-HPLC) in an Agilent 1200 HPLC system equipped with a diode array UV detector. Separation was conducted using an Waters Xterra RP8 column (Waters Corporation) and a mobile- 31 Adsorption isotherms to evaluate the adsorption of Ser E rMOMP to the different phosphate-treated SPA08 were conducted by titration of the desired adjuvant with increasing concentrations of Ser E rMOMP in Tris buffer saline pH 7.4. SPA08 adjuvants with different degrees of phosphate substitution were prepared by addition of E6020 to AlOOH followed by addition of phosphate to reach the desired P/Al ratio.…”

Section: Adsorption Isothermsmentioning

confidence: 99%

Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis

Visan

Sanchez

Kania

et al. 2016

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Chlamydia trachomatis is one of the most common sexually transmitted pathogens and the development of an effective vaccine is highly desirable. The Major Outer Membrane Protein (MOMP) is one of the most abundant and immunogenic chlamydial proteins. Here we investigated the effects of phosphate substitution on the physicochemical and immunochemical properties of an experimental vaccine composed of serovar E recombinant MOMP (rMOMP) and a proprietary adjuvant system SPA08, consisting of aluminum oxyhydroxide (AlOOH) containing the TLR4 agonist E6020.An increase in phosphate substitution in the AlOOH component of the adjuvant markedly decreased the adsorptive coefficient and adsorptive capacity for both Ser E rMOMP and E6020. In vaccine formulations used for immunizations, phosphate substitution induced a decrease in the % adsorption of Ser E rMOMP without affecting the % adsorption of E6020.Immunogenicity studies in CD1 mice showed that an increase in phosphate substitution of the SPA08 adjuvant resulted in an increase in Ser E rMOMP-specific serum total IgG and IgG1 but not IgG2a titers. The degree of phosphate substitution in SPA08 also significantly increased in vitro neutralization concomitant with a decrease in proinflammatory cytokines secreted by Ser E rMOMP-restimulated splenocytes.Taken together, the results of these studies suggest that the degree of phosphate substitution in AlOOH greatly affects the adsorption of E6020 and Ser E rMOMP to AlOOH resulting in significant effects on vaccine-induced cellular and humoral responses.

show abstract

“…Recombinant PcpA, PhtD, and PlyD1 proteins, constructed from a serotype 6B S. pneumoniae strain, were obtained from Sanofi Pasteur. Protein doses previously described as optimal in BALB/c mice (25) and determined to be optimal in our preliminary work in C57BL/6 mice were combined with aluminum hydroxide (alum) as an adjuvant. Unvaccinated controls received alum alone.…”

Section: Animalsmentioning

confidence: 99%

Contributions to Protection from Streptococcus pneumoniae Infection Using the Monovalent Recombinant Protein Vaccine Candidates PcpA, PhtD, and PlyD1 in an Infant Murine Model during Challenge

Verhoeven

Perry

Pichichero

2014

Clin. Vaccine Immunol.

View full text Add to dashboard Cite

A vaccine consisting of several conserved proteins with different functions directing the pathogenesis of pneumonia and sepsis would be preferred for protection against infection by Streptococcus pneumoniae. Infants will be the major population targeted for nextgeneration pneumococcal vaccines. Here, we investigated the potential efficacy provided by three recombinant pneumococcal vaccine candidate proteins-pneumococcal histidine triad D (PhtD), detoxified pneumolysin derivative (PlyD1), and pneumococcal choline-binding protein A (PcpA)-for reducing pneumonia and sepsis in an infant mouse vaccine model. We found vaccination with PhtD and PcpA provided high IgG antibody titers after vaccination in infant mice, similar to adult mice comparators. PlyD1-specific total IgG was significantly lower in infant mice, with minimal boosting with the second and third vaccinations. Similar isotypes of IgG for PhtD and PlyD1 were generated in infant compared to adult mice. Although lower total specific IgG to all three proteins was elicited in infant than in adult mice, the infant mice were protected from bacteremic pneumonia and sepsis mortality (PlyD1) and had lower lung bacterial burdens (PcpA and PhtD) after challenge. The observed immune responses coupled with bacterial reductions elicited by each of the monovalent proteins support further testing in human infant clinical trials.

show abstract

Formulation, stability and immunogenicity of a trivalent pneumococcal protein vaccine formulated with aluminum salt adjuvants

Cited by 36 publications

References 39 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

Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis

Contributions to Protection from Streptococcus pneumoniae Infection Using the Monovalent Recombinant Protein Vaccine Candidates PcpA, PhtD, and PlyD1 in an Infant Murine Model during Challenge

Contact Info

Product

Resources

About