Evaluation of the immune response to RTS,S/AS01 and RTS,S/AS02 adjuvanted vaccines

Leroux‐Roels, Geert; Leroux-Roels, Isabel; Clement, Frédéric; Ofori-Anyinam, Opokua; Lievens, Marc; Jongert, Erik; Moris, Philippe; Ballou, W. Ripley; Cohen, Joe

doi:10.4161/hv.29375

Cited by 58 publications

(39 citation statements)

References 30 publications

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“…The choice of adjuvant was reconsidered following evidence in larger studies conducted in adult volunteers, and subsequently in children, of improved CD4 + T-cell responses and improved efficacy when AS01 was used instead of AS02 [41][42][43][44][45]. In a large Phase-3 study, efficacy against any malaria due to P. falciparum over 12 months of follow-up after dose 3 was 31.3% in infants 6-12 weeks of age with coadministration of EPI (Expanded Program on Immunization) vaccines and 55.8% in children 5-17 months of age at the time of the first dose [46].…”

Section: Rtss/as01 Malaria Vaccine Candidatementioning

confidence: 99%

Adjuvant system AS01: helping to overcome the challenges of modern vaccines

Didierlaurent

Laupèze

Pasquale

et al. 2016

Expert Review of Vaccines

383

286

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Introduction: Adjuvants are used to improve vaccine immunogenicity and efficacy by enhancing antigen presentation to antigen-specific immune cells with the aim to confer long-term protection against targeted pathogens. Adjuvants have been used in vaccines for more than 90 years. Combinations of immunostimulatory molecules, such as in the Adjuvant System AS01, have opened the way to the development of new or improved vaccines. Areas covered: AS01 is a liposome-based vaccine adjuvant system containing two immunostimulants: 3-O-desacyl-4ʹ-monophosphoryl lipid A (MPL) and the saponin QS-21. Here we describe studies investigating the mode of action of AS01, and consider the role of AS01 in enhancing specific immune responses to the antigen for selected candidate vaccines targeting malaria and herpes zoster. The effects of AS01 are rapid and transient, being localized to the injected muscle and draining lymph node. AS01 is efficient at promoting CD4 + T cell-mediated immune responses and is an appropriate candidate adjuvant for inclusion in vaccines targeting viruses or intracellular pathogens. Expert commentary: AS01 activity to enhance adaptive responses depends on synergistic activities of QS-21 and MPL. AS01 adjuvantation shows good prospects for use in new vaccines targeted to populations with challenging immune statuses and against diseases caused by complex pathogens. ARTICLE HISTORY

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Section: Rtss/as01 Malaria Vaccine Candidatementioning

confidence: 99%

Adjuvant system AS01: helping to overcome the challenges of modern vaccines

Didierlaurent

Laupèze

Pasquale

et al. 2016

Expert Review of Vaccines

383

286

View full text Add to dashboard Cite

show abstract

“…to improve the magnitude and duration of the immune responses to CSP [15]. The Adjuvant System selected [15], AS01, consists of two immunostimulants, 3-O-desacyl-4 -monophosphoryl lipid A (MPL) and QS-21 Stimulon ® Adjuvant (QS-21), in a liposome formulation.…”

Section: Circumsporozoite Protein and Rtssmentioning

confidence: 99%

“…The Adjuvant System selected [15], AS01, consists of two immunostimulants, 3-O-desacyl-4 -monophosphoryl lipid A (MPL) and QS-21 Stimulon ® Adjuvant (QS-21), in a liposome formulation. Recent studies suggest that one mechanism of action of AS01 is to transiently stimulate the innate immune system and activate a high number of efficient antigen-presenting dendritic cells in the draining lymph nodes [16].…”

Section: Circumsporozoite Protein and Rtssmentioning

confidence: 99%

RTS,S: Toward a first landmark on the Malaria Vaccine Technology Roadmap

Kaslow

Biernaux

2015

Vaccine

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The Malaria Vaccine Technology Roadmap calls for a 2015 landmark goal of a first-generation malaria vaccine that has protective efficacy against severe disease and death, lasting longer than one year. This review focuses on product development efforts over the last five years of RTS,S, a pre-erythrocytic, recombinant subunit, adjuvanted, candidate malaria vaccine designed with this goal of a first-generation malaria vaccine in mind. RTS,S recently completed a successful pivotal Phase III safety, efficacy and immunogenicity study. Although vaccine efficacy was found to be modest, a substantial number of cases of clinical malaria were averted over a 3-4 years period, particularly in settings of significant disease burden. European regulators have subsequently adopted a positive opinion under the Article 58 procedure for an indication of active immunization of children aged 6 weeks up to 17 months against malaria caused by Plasmodium falciparum and against hepatitis B. Further evaluations of the benefit, risk, feasibility and cost-effectiveness of RTS,S are now anticipated through policy and financing reviews at the global and national levels.

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“…MPL stimulates TLR4 with the subsequent induction of a Th1-mediated response and antibody production (see above), QS21 promotes antibody generation and CD8+ T cell activation, and the liposomes or emulsion stimulate antigen uptake from the APC such as dendritic cells [76,77]. The VLP-based vaccine against malaria RTS,S (Mosquirix, GSK) has shown a better immune response and improved efficacy in several clinical trials when formulated with AS01 in comparison with AS02 [78,79]. AS01 has been tested in clinical trials with the tetravalent HPV VLP-vaccine (GSK) [80] showing a significant effect in broadening vaccine efficacy and enhancing cross-reactivity.…”

Section: Classes Of Adjuvants Tested For Vlp-based Vaccinesmentioning

confidence: 99%

Adjuvant formulations for virus-like particle (VLP) based vaccines

Cimica

Galarza

2017

Clinical Immunology

102

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The development of virus-like particle (VLP) technology has had an enormous impact on modern vaccinology. In order to optimize the efficacy and safety of VLP-based vaccines, adjuvants are included in most vaccine formulations. To date, most licensed VLP-based vaccines utilize the classic aluminum adjuvant compositions. Certain challenging pathogens and weak immune responder subjects may require further optimization of the adjuvant formulation to maximize the magnitude and duration of the protective immunity. Indeed, novel classes of adjuvants such as liposomes, agonists of pathogen recognition receptors, polymeric particles, emulsions, cytokines and bacterial toxins, can be used to optimize the immunostimulatory activity of a VLP-based vaccine. This review describes the current advances in adjuvant technology for VLP-based vaccines directed at viral diseases, and discusses the basic principles for designing adjuvant formulations for enhancing the vaccine immunogenicity.

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Evaluation of the immune response to RTS,S/AS01 and RTS,S/AS02 adjuvanted vaccines

Cited by 58 publications

References 30 publications

Adjuvant system AS01: helping to overcome the challenges of modern vaccines

Adjuvant system AS01: helping to overcome the challenges of modern vaccines

RTS,S: Toward a first landmark on the Malaria Vaccine Technology Roadmap

Adjuvant formulations for virus-like particle (VLP) based vaccines

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