Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs

Francica, Joseph R.; Zak, Daniel E.; Linde, Caitlyn; Siena, Emilio; Johnson, Carrie D.; Juraska, Michal; Yates, Nicole L.; Gunn, Bronwyn M.; Gregorio, Ennio De; Flynn, Barbara J.; Valiante, Nicholas M.; Malyala, Padma; Barnett, Susan W.; Sarkar, Pampi; Singh, Manmohan; Jain, Siddhartha; Ackerman, Margaret E.; Alam, Munir; Ferrari, Guido; Salazar, Andrés M.; Tomaras, Georgia D.; O’Hagan, Derek T.; Aderem, Alan; Alter, Galit; Seder, Robert A.

doi:10.1182/bloodadvances.2017011411

Cited by 82 publications

(79 citation statements)

References 94 publications

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“…For example, we recently published a study in non-human primates that evaluated a number of alternative adjuvants, including AH, with a recombinant HIV env protein, in which the relative lack of potency of the aluminum-adjuvanted vaccine was clear. 144 Nevertheless, we strongly believe that aluminum adjuvants remain a key benchmark and a “gold standard”, against which new adjuvants can and should be routinely evaluated. The safety and potency of aluminum adjuvants has been established in man, in combination with many vaccines, over decades, involving billions of doses, and the accumulated experience represents an important and substantive “body of evidence”.…”

Section: Future Directions Of Aluminum Adjuvantsmentioning

confidence: 99%

Optimizing the utilization of aluminum adjuvants in vaccines: you might just get what you want

2018

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Aluminum-containing adjuvants have been used for over 90 years to enhance the immune response to vaccines. Recent work has significantly advanced our understanding of the physical, chemical, and biological properties of these adjuvants, offering key insights on underlying mechanisms. Given the long-term success of aluminum adjuvants, we believe that they should continue to represent the “gold standard” against which all new adjuvants should be compared. New vaccine candidates that require adjuvants to induce a protective immune responses should first be evaluated with aluminum adjuvants before other more experimental approaches are considered, since use of established adjuvants would facilitate both clinical development and the regulatory pathway. However, the continued use of aluminum adjuvants requires an appreciation of their complexities, in combination with access to the necessary expertise to optimize vaccine formulations. In this article, we will review the properties of aluminum adjuvants and highlight those elements that are critical to optimize vaccine performance. We will discuss how other components (excipients, TLR ligands, etc.) can affect the interaction between adjuvants and antigens, and impact the potency of vaccines. This review provides a resource and guide, which will ultimately contribute to the successful development of newer, more effective and safer vaccines.

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Section: Future Directions Of Aluminum Adjuvantsmentioning

confidence: 99%

Optimizing the utilization of aluminum adjuvants in vaccines: you might just get what you want

2018

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“…This disconnect may be related to the ability of MF59 to significantly augment neutralization and antibody function that appears to harbor a functional "hole" in NK cell and monocyte activation (Figure 3). Given our emerging appreciation for opportunities to combine adjuvants because of their complementary immune-stimulating capabilities (44,65,66), defining the landscape of qualitative modifications induced by individual and combined adjuvants may offer an opportunity to fully control the quantity and quality of the humoral immune response. Thus, with our growing appreciation for the importance of particular Fc-effector functions across infections (15,(51)(52)(53)(54)(55), next-generation rational vaccine design efforts may benefit from a comprehensive understanding of the functional impact and opportunities to conditionally elicit vaccine-induced antibody effector function to maximize the potency of the antigen-binding and constant domaindriven function of vaccine-induced antibodies.…”

Section: Discussionmentioning

confidence: 99%

Selective induction of antibody effector functional responses using MF59-adjuvanted vaccination

Boudreau¹,

Yu²,

Suscovich³

et al. 2019

Journal of Clinical Investigation

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“…The partial dissociation of IFN-g and proliferative responses on one side and of responses induced by immunization against hPPI and upon induction of diabetes by pI:C on the other side was not unexpected. Adjuvantmediated immunization and pI:C indeed involve different pathways in antigen-presenting cells and CD4 + T-cell activation (35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

Humanized Mouse Model to Study Type 1 Diabetes

et al. 2018

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Key requirements in type 1 diabetes (T1D) are in setting up new assays as diagnostic biomarkers that will apply to prediabetes, likely T-cell assays, and in designing antigen-specific therapies to prevent T1D development. New preclinical models of T1D will be required to help with advancing both aims. By crossing mouse strains that lack either murine MHC class I and class II genes and insulin genes, we developed YES mice that instead express human HLA-A*02:01, HLA-DQ8, and insulin genes as transgenes. The metabolic and immune phenotype of YES mice is basically identical to that of the parental strains. YES mice remain insulitis and diabetes free up to 1 year of follow-up, maintain normoglycemia to an intraperitoneal glucose challenge in the long-term range, have a normal β-cell mass, and show normal immune responses to conventional antigens. This new model has been designed to evaluate adaptive immune responses to human insulin on a genetic background that recapitulates a human high-susceptibility HLA-DQ8 genetic background. Although insulitis free, YES mice develop T1D when challenged with polyinosinic-polycytidylic acid. They allow the characterization of preproinsulin epitopes recognized by CD8 and CD4 T cells upon immunization against human preproinsulin or during diabetes development.

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Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs

Abstract: Key Points• TLR4 and 7 agonists improve titers when coformulated with alum but not an emulsion formulation, but do not impact the titer halflives.• Alum/TLR7 and pIC:LC are potent adjuvant formulations that improve the magnitude and quality of humoral and cellular responses to HIV Env.

Cited by 82 publications

References 94 publications

Optimizing the utilization of aluminum adjuvants in vaccines: you might just get what you want

Optimizing the utilization of aluminum adjuvants in vaccines: you might just get what you want

Selective induction of antibody effector functional responses using MF59-adjuvanted vaccination

Humanized Mouse Model to Study Type 1 Diabetes

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