Dose ranging of adjuvant and antigen in a cell culture H5N1 influenza vaccine: Safety and immunogenicity of a phase 1/2 clinical trial

Keitel, Wendy A.; Groth, Nicola; Lattanzi, Maria; Praus, Michaela; Hilbert, Anne Katrin; Borkowski, Astrid; Tsai, Ted

doi:10.1016/j.vaccine.2009.10.019

Cited by 69 publications

(46 citation statements)

References 25 publications

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“…It has been shown to be effective for a HCV vaccine [133]. It can initiate greater, longer-lasting, and broader immune responses than a nonadjuvanted split flu vaccine in healthy young children [134,135] and in adults [136]. As an adjuvant for flu vaccine, it is more potent than aluminum-based adjuvants in terms of both antibody and T-cell responses [131].…”

Section: Emulsionsmentioning

confidence: 99%

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Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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Section: Emulsionsmentioning

confidence: 99%

“…CEL-1000 (18-mer) is an analogue of peptide G (a peptide from human MHCII beta chain, aa [135][136][137][138][139][140][141][142][143][144][145][146][147][148][149], which is known to enhance immune responses of other immunogenic peptides. They can be conjugated to HIV (HGP-30) and malaria peptides as potential vaccines.…”

Section: Specific Peptides/proteinsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…However, until recently, only a few reports regarding the motivation for selecting this squalene concentration were published (9,21,25). Moreover, a recent study showed that dilution of MF59 did not compromise the immune response in a pandemic influenza vaccine clinical trial (20). If adjuvant activity can be maintained with a reduction of the squalene dose, then the local reactogenicity of o/w emulsions can potentially be reduced.…”

mentioning

confidence: 99%

Effects on Immunogenicity by Formulations of Emulsion-Based Adjuvants for Malaria Vaccines

Fox¹,

Baldwin²,

Vedvick³

et al. 2012

Clin. Vaccine Immunol.

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bNew malaria vaccines are urgently needed to improve vaccine protective efficacy. PfCelTOS is a recombinant malaria vaccine antigen that has shown protective efficacy in a small-animal challenge model when combined with a water-in-oil emulsion adjuvant (Montanide ISA 720). In this report, we show that PfCelTOS vaccines containing GLA-SE (a stable oil-in-water emulsion combined with a Toll-like receptor 4 [TLR4] agonist) elicit strong Th1-type immune responses in BALB/c mice. These responses include higher antigen-specific IgG2a antibody titers and more gamma interferon (IFN-␥) production than those seen with a PfCelTOS vaccine containing Montanide ISA 720. Furthermore, reducing the emulsion dose from 2% to 1% or 0.5% (vol/vol) squalene in GLA-SE did not compromise immunogenicity. Emulsion dose titration in the absence of formulated GLA caused some reduction in humoral and cellular immune responses compared to those with the 2% squalene emulsion dose. Oil-in-water (o/w) emulsions have been used safely and successfully as adjuvants in modern vaccines. The most notable o/w emulsions are MF59 and AS03, which are produced by Novartis and GSK Biologicals, respectively. Both of these adjuvants contain squalene at ϳ2.5% (vol/vol) in the final vaccine formulation (13). However, until recently, only a few reports regarding the motivation for selecting this squalene concentration were published (9,21,25). Moreover, a recent study showed that dilution of MF59 did not compromise the immune response in a pandemic influenza vaccine clinical trial (20). If adjuvant activity can be maintained with a reduction of the squalene dose, then the local reactogenicity of o/w emulsions can potentially be reduced. Furthermore, the vaccine cost could decrease while the available adjuvant supply would increase, thus making vaccine and adjuvant production in resource-poor countries more achievable.The recombinant malaria antigen PfCelTOS (Plasmodium falciparum cell traversal protein for ookinetes and sporozoites) combined with an emulsion adjuvant (Montanide ISA 720) protected 60% of mice in a heterologous challenge model (8). PfCelTOS inhibits sporozoite motility and hepatocyte infectivity and could be an important component of new malaria vaccines. Both cellular and humoral immune responses are important for protective efficacy directed against this antigen (7,8).In this work, we evaluated squalene-based stable emulsion (SE) adjuvant dose effects on humoral and cellular immune responses to PfCelTOS. Moreover, we investigated the effect of including a formulated synthetic Toll-like receptor 4 (TLR4) agonist, glucopyranosyl lipid adjuvant (GLA), in the vaccine formulation. We show that squalene concentrations of Ͻ2% (vol/vol) in GLA-SE may induce adjuvant responses equivalent to those seen with a 2% (vol/vol) squalene concentration. This finding has important implications for vaccine adjuvant production and dosing as well as for novel routes of administration (such as intradermal routes), which may be more sensitive to oil concentrations. Mo...

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“…4 [5][6][7][8][9][10][11][12][13][14][15] There are pre-clinical reasons to believe that improvements to the vaccine seed virus generation process could lead to clinical improvements in cell culture-based vaccines.…”

Section: Fully Mammalian Cell Culture-based Influenza Vaccinesmentioning

confidence: 99%