Association Between Immunogenicity and Adsorption of a Recombinant<i>Streptococcus pneumoniae</i>Vaccine Antigen by an Aluminum Adjuvant

Levesque, Philip; Foster, K. Wade; Alwis, Uditha de

doi:10.4161/hv.2.2.2645

Cited by 19 publications

(12 citation statements)

References 21 publications

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“…Berthold et al [34] concluded that adsorption of recombinant anthrax protective antigen to aluminum phosphate enhances the immunogenicity of lower doses of antigen. Levesque et al [35] also concluded that increased adsorption to adjuvant correlates with greater antigenicity of the proteins studied.…”

Section: Discussionmentioning

confidence: 95%

Improved formulation of a recombinant ricin A-chain vaccine increases its stability and effective antigenicity

Carra

Wannemacher

Tammariello

et al. 2007

Vaccine

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Section: Discussionmentioning

confidence: 95%

Improved formulation of a recombinant ricin A-chain vaccine increases its stability and effective antigenicity

Carra

Wannemacher

Tammariello

et al. 2007

Vaccine

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“…We then compared vaccine formulations with AH, with fully adsorbed L1V (with or without CpG), to vaccine formulations with phosphate-buffer treated aluminum hydroxide (PTAH), which did not significantly adsorb L1V. Similar to other studies that investigated the immune response to adsorbed antigens like recombinant protective antigen from anthrax [11] or recombinant antigens from Streptococcus pneumonia [37], we too consistently found that the L1V antigen adsorbed to an aluminum salt gave enhanced antibody-responses and better protection after VACV-challenge when compared to formulations that had L1V free in solution in the presence of AH (i.e., unbound LIV). The mechanism of why L1V gives enhanced antibody responses when adsorbed to AH is not known and will require further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…This conformational destabilization was seen previously for some model protein antigens [38, 39], but antibody responses were not ascertained. Alternatively, Levesque et al hypothesized that the differences in antibody responses that they saw with recombinant antigens from Streptococcus pneumonia may have been due to initially higher localized concentration of antigen in proximity with adjuvant when antigen was adsorbed to AH [37]. …”

Section: Discussionmentioning

confidence: 99%

Adsorption of recombinant poxvirus L1-protein to aluminum hydroxide/CpG vaccine adjuvants enhances immune responses and protection of mice from vaccinia virus challenge

Xiao

Zeng

Alexander

et al. 2013

Vaccine

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The stockpiling of live vaccinia virus vaccines has enhanced biopreparedness against the intentional or accidental release of smallpox. Ongoing research on future generation smallpox vaccines is providing key insights into protective immune responses as well as important information about subunit vaccine design strategies. For protein-based recombinant subunit vaccines, the formulation and stability of candidate antigens with different adjuvants are important factors to consider for vaccine design. In this work, a non-tagged secreted L1-protein, a target antigen on mature virus, was expressed using recombinant baculovirus technology and purified. To identify optimal formulation conditions for L1, a series of biophysical studies was performed over a range of pH and temperature conditions. The overall physical stability profile was summarized in an empirical phase diagram. Another critical question to address for development of an adjuvanted-vaccine was if immunogenicity and protection could be affected by the interactions and binding of L1 to aluminum salts (Alhydrogel) with and without a second adjuvant, CpG. We thus designed a series of vaccine formulations with different binding interactions between the L1 and the two adjuvants, and then performed a series of vaccination-challenge experiments in mice including measurement of antibody responses and post-challenge weight-loss and survival. We found that better humoral responses and protection were conferred with vaccine formulations when the L1-protein was adsorbed to Alhydrogel. These data demonstrate that designing vaccine formulation conditions to maximize antigen-adjuvant interactions is a key factor in smallpox subunit vaccine immunogenicity and protection.

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“…The exact mechanism of action is an area of ongoing research but the major contribution to adjuvanticity is the depot effect of antigen (Ag) adsorbed to the adjuvant, that is stored for an extended time at the site of injection and is thus available at comparatively high concentrations for uptake by phagocytic cells (Guy, 2007; Harrison, 1935). Activation and recruitment of antigen-presenting cells, which play a key role in the amplification and differentiation of antigen-specific T-cells, also explain the immunological phenomena triggered by alum (Levesque et al, 2006). …”

Section: Influenza Vaccines Strategiesmentioning

confidence: 99%

H5N1 vaccines in humans

et al. 2013

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The spread of highly pathogenic avian H5N1 influenza viruses since 1997 and their virulence for poultry and humans has raised concerns about their potential to cause an influenza pandemic. Vaccines offer the most viable means to combat a pandemic threat. However, it will be a challenge to produce, distribute and implement a new vaccine if a pandemic spreads rapidly. Therefore, efforts are being undertaken to develop pandemic vaccines that use less antigen and induce cross-protective and long-lasting responses, that can be administered as soon as a pandemic is declared or possibly even before, in order to prime the population and allow for a rapid and protective antibody response. In the last few years, several vaccine manufacturers have developed candidate pandemic and pre-pandemic vaccines, based on reverse genetics and have improved the immunogenicity by formulating these vaccines with different adjuvants. Some of the important and consistent observations from clinical studies with H5N1 vaccines are as follows: two doses of inactivated vaccine are generally necessary to elicit the level of immunity required to meet licensure criteria, less antigen can be used if an oil-in-water adjuvant is included, in general antibody titers decline rapidly but can be boosted with additional doses of vaccine and if high titers of antibody are elicited, cross-reactivity against other clades is observed. Prime-boost strategies elicit a more robust immune response. In this review, we discuss data from clinical trials with a variety of H5N1 influenza vaccines. We also describe studies conducted in animal models to explore the possibility of reassortment between pandemic live attenuated vaccine candidates and seasonal influenza viruses, since this is an important consideration for the use of live vaccines in a pandemic setting.

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Association Between Immunogenicity and Adsorption of a RecombinantStreptococcus pneumoniaeVaccine Antigen by an Aluminum Adjuvant

Cited by 19 publications

References 21 publications

Improved formulation of a recombinant ricin A-chain vaccine increases its stability and effective antigenicity

Improved formulation of a recombinant ricin A-chain vaccine increases its stability and effective antigenicity

Adsorption of recombinant poxvirus L1-protein to aluminum hydroxide/CpG vaccine adjuvants enhances immune responses and protection of mice from vaccinia virus challenge

H5N1 vaccines in humans

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