Effect of the strength of adsorption of HIV 1 SF162dV2gp140 to aluminum‐containing adjuvants on the immune response

Hansen, Bethany; Malyala, Padma; Singh, Manmohan; Sun, Yuliang; Srivastava, Indresh K.; HogenEsch, Harm; Hem, Stanley L.

doi:10.1002/jps.22555

Cited by 28 publications

(16 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, enhanced immunogenicity was seen when a recombinant Candida antigen (rAls3p-N) was diluted with phosphate-buffered saline versus saline alone (44). Similarly, phosphate modulation of aluminum oxyhydroxide in both hepatitis B surface antigen and HIV-1 (SF162dV2gp140) subunit vaccines demonstrated enhancement of immunogenicity (8,9).…”

Section: Discussionmentioning

confidence: 99%

“…These effects include NLRP3 inflammasome activation, prostaglandin production, release of endogenous danger signals such as uric acid or DNA following cell death, binding to membrane lipids, and B cell priming (6,7). In a series of papers, Hansen and colleagues showed that the strength of antigen adsorption to an aluminum-containing adjuvant is inversely related to the immune response (8)(9)(10). They also showed that antigens do not need to be bound to the aluminum salt in order to benefit from the adjuvant effect (11) and that interstitial fluid can contribute to dissociation of the antigen-adjuvant complex in newly formulated vaccines but less so in older samples (12).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions

Watkinson

Soliakov

Ganesan³

et al. 2013

Clin Vaccine Immunol

View full text Add to dashboard Cite

f Aluminum salts are the most widely used vaccine adjuvants, and phosphate is known to modulate antigen-adjuvant interactions. Here we report an unexpected role for phosphate buffer in an anthrax vaccine (SparVax) containing recombinant protective antigen (rPA) and aluminum oxyhydroxide (AlOH) adjuvant (Alhydrogel). Phosphate ions bind to AlOH to produce an aluminum phosphate surface with a reduced rPA adsorption coefficient and binding capacity. However, these effects continued to increase as the free phosphate concentration increased, and the binding of rPA changed from endothermic to exothermic. Crucially, phosphate restored the thermostability of bound rPA so that it resembled the soluble form, even though it remained tightly bound to the surface. Batches of vaccine with either 0.25 mM (subsaturated) or 4 mM (saturated) phosphate were tested in a disease model at batch release, which showed that the latter was significantly more potent. Both formulations retained their potency for 3 years. The strongest aluminum adjuvant effects are thus likely to be via weakly attached or easily released native-state antigen proteins.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions

Watkinson

Soliakov

Ganesan³

et al. 2013

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…Such adsorption of antigen was thought mechanistically to provide a depot effect that permits prolonged exposure to the antigen, although immune cell recruitment to the injection site and enhanced antigen uptake are now known to play key roles [4]. While antigen adsorption to aluminum has long been considered to be a key step in vaccine immunogenicity, a growing body of literature has shown that the strength of antigen adsorption is important [5–8]. In fact, there are several examples where no differences in antibody-response have been seen between adsorbed and non-adsorbed protein formulated with aluminum [9–13].…”

Section: Introductionmentioning

confidence: 99%

“…Non-adsorbed protein could also be retained in void spaces of aluminum [12]. Additionally, detailed studies have shown that the more tightly an antigen is bound to aluminum, the poorer the immune response [5–8, 13]. …”

Section: Introductionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…The assessment of adsorption isotherms has typically been conducted manually using sample volumes of a few milliliters 9,[15][16][17][18] and hence, this process requires a large amount of antigen and is labor-intensive. High-throughput technologies are less labor-intensive, they can provide more rapid assessments over a wider range of experimental conditions and they use smaller sample volumes, 19,20 thus reducing costs.…”

Section: Introductionmentioning

confidence: 99%

Development of a High-Throughput Screening Platform to Study the Adsorption of Antigens onto Aluminum-Containing Adjuvants

Jully

Moniotte

Mathot

et al. 2015

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Effect of the strength of adsorption of HIV 1 SF162dV2gp140 to aluminum‐containing adjuvants on the immune response

Cited by 28 publications

References 16 publications

Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions

Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions

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

Development of a High-Throughput Screening Platform to Study the Adsorption of Antigens onto Aluminum-Containing Adjuvants

Contact Info

Product

Resources

About