Recent clinical experience with vaccines using MPL- and QS-21-containing Adjuvant Systems

Garçon, Nathalie; Mechelen, Marcelle Van

doi:10.1586/erv.11.29

Cited by 277 publications

(204 citation statements)

References 177 publications

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“…proprietary Adjuvant Systems containing the immunostimulants monophosphoryl lipid A, a detoxified derivative of LPS (5), and the saponin QS21 (6). M72 is a fusion protein derived from Mtb32A and Mtb39A, antigens present in Mtb and BCG.…”

Section: What This Study Adds To the Fieldmentioning

confidence: 99%

Induction and Regulation of T-Cell Immunity by the Novel Tuberculosis Vaccine M72/AS01 in South African Adults

Day

Tameris

Mansoor

et al. 2013

Am J Respir Crit Care Med

106

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Rationale: Tuberculosis (TB) is a major cause of morbidity and mortality worldwide, thus there is an urgent need for novel TB vaccines. Objectives: We investigated a novel TB vaccine candidate, M72/ AS01, in a phase IIa trial of bacille Calmette-Gué rin-vaccinated, HIV-uninfected, and Mycobacterium tuberculosis (Mtb)-infected and -uninfected adults in South Africa. Methods: Two doses of M72/AS01 were administered to healthy adults, with and without latent Mtb infection. Participants were monitored for 7 months after the first dose; cytokine production profiles, cell cycling, and regulatory phenotypes of vaccine-induced T cells were measured by flow cytometry. Measurements and Main Results: The vaccine had a clinically acceptable safety profile, and induced robust, long-lived M72-specific T-cell and antibody responses. M72-specific CD4 T cells produced multiple combinations of Th1 cytokines. Analysis of T-cell Ki67 expression showed that most vaccination-induced T cells did not express Th1 cytokines or IL-17; these cytokine-negative Ki67 1 T cells included subsets of CD4 T cells with regulatory phenotypes. PD-1, a negative regulator of activated T cells, was transiently expressed on M72-specific CD4 T cells after vaccination. Specific T-cell subsets were present at significantly higher frequencies after vaccination of Mtb-infected versus -uninfected participants. Conclusions: M72/AS01 is clinically well tolerated in Mtb-infected and -uninfected adults, induces high frequencies of multifunctional T cells, and boosts distinct T-cell responses primed by natural Mtb infection. Moreover, these results provide important novel insights into how this immunity may be appropriately regulated after novel TB vaccination of Mtb-infected and -uninfected individuals. Clinical trial registered with www.clinicaltrials.gov (NCT 00600782).Keywords: tuberculosis; vaccine; T cell; cytokine; proliferation Tuberculosis (TB) remains a major cause of morbidity and mortality, with approximately 9 million new cases and 1.5 million deaths worldwide each year (1). Bacille Calmette-Guérin (BCG) provides protection against miliary TB and TB meningitis in children (2); however, BCG provides variable efficacy against pulmonary TB in adults (3), the most common clinical manifestation of the disease. Mycobacterium tuberculosis (Mtb) is transmitted primarily by adults; therefore novel, effective TB vaccines are urgently needed to target this population, and thereby reduce the burden of TB disease worldwide.Phase I and II clinical trials of several novel candidate TB vaccines have either been completed or are currently ongoing (4). These vaccines include the candidate recombinant fusion protein vaccine M72, formulated with GlaxoSmithKline Vaccines Approximately one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), and despite the widespread use of the bacille Calmette-Guérin vaccine, tuberculosis (TB) remains a major cause of morbidity and mortality. There is an urgent need to develop novel TB vaccines that are safe,...

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Section: What This Study Adds To the Fieldmentioning

confidence: 99%

Induction and Regulation of T-Cell Immunity by the Novel Tuberculosis Vaccine M72/AS01 in South African Adults

Day

Tameris

Mansoor

et al. 2013

Am J Respir Crit Care Med

106

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“…The adjuvant AS01 B is thought to play a key role in the response to the F4/AS01 B investigational vaccine by activating the innate immune system due to its immunostimulatory components MPL, a TLR4 agonist, and the saponin QS-21 (28,29). Here, the potential impact of chloroquine on the response induced by the adjuvant was assessed by measuring the ability of PBMCs to secrete IL-6 upon incubation with MPL and QS-21.…”

Section: Demographicsmentioning

confidence: 99%

Immunogenicity and Safety of a Booster Dose of an Investigational Adjuvanted Polyprotein HIV-1 Vaccine in Healthy Adults and Effect of Administration of Chloroquine

Leroux‐Roels

Bourguignon

Willekens

et al. 2014

Clin Vaccine Immunol

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“…Ligation of intracellular TLRs is especially effective at promoting IL-12 production from innate immune cells, which promotes development of Th1 responses that are crucial for protection against viruses, tumors and intracellular bacteria. Consequently, TLR ligands have considerable potential as adjuvants for infectious disease vaccines and the TLR4 ligand MPL has already been licensed for use in humans [12].…”

Section: Introductionmentioning

confidence: 99%

Addition of a TLR7 agonist to an acellular pertussis vaccine enhances Th1 and Th17 responses and protective immunity in a mouse model

Misiak

Leuzzi

Allen

et al. 2017

Vaccine

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a b s t r a c tA resurgence of whooping cough (pertussis) has been observed in recent years in a number of developed countries, despite widespread vaccine coverage. Although the exact reasons of the recurrence of pertussis are not clear, there are a number of potential causes, like antigenic variation in the circulating strains of Bordetella pertussis, changes in surveillance and diagnostic tools, and potential differences in protection afforded by current acellular pertussis (aP) vaccines compared to more reactogenic whole cell (wP) vaccines, which they replaced. Studies in animal models have shown that induction of cellular as well as humoral immune responses are key to conferring effective and long lasting protection against B. pertussis. wP vaccines induce robust Th1/Th17 responses, which are associated with good protection against lung infection. In contrast, aP vaccines induce mixed Th2/Th17 responses. One research option is to modify current aP vaccines with the intention of inducing protective T cell responses, without compromising on their low reactogenicity profile. Here we found that formulation of an aP vaccine with a novel adjuvant based on a Toll-like receptor 7 agonist (TLR7a) adsorbed to aluminum hydroxide (alum) enhanced B. pertussis-specific Th1 and Th17 responses and serum IgG2a/b antibodies, which had greater functional capacity than those induced by aP formulated with alum alone. Furthermore, addition of a TLR7a enhanced the protective efficacy of the aP vaccine against B. pertussis aerosol challenge; protection was comparable to that of a wP vaccine. These findings suggest that alum-TLR7a is a promising adjuvant for clinical development of next generation pertussis vaccines.

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Recent clinical experience with vaccines using MPL- and QS-21-containing Adjuvant Systems

Cited by 277 publications

References 177 publications

Induction and Regulation of T-Cell Immunity by the Novel Tuberculosis Vaccine M72/AS01 in South African Adults

Induction and Regulation of T-Cell Immunity by the Novel Tuberculosis Vaccine M72/AS01 in South African Adults

Immunogenicity and Safety of a Booster Dose of an Investigational Adjuvanted Polyprotein HIV-1 Vaccine in Healthy Adults and Effect of Administration of Chloroquine

Addition of a TLR7 agonist to an acellular pertussis vaccine enhances Th1 and Th17 responses and protective immunity in a mouse model

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