Environmental modifiers of RTS,S/AS01 malaria vaccine efficacy in Lilongwe, Malawi

Bell, Griffin J.; Loop, Matthew Shane; Mvalo, Tisungane; Juliano, Jonathan J.; Mofolo, Innocent; Kamthunzi, Portia; Tegha, Gerald; Lievens, Marc; Bailey, Jeffrey A.; Emch, Michael; Hoffman, Irving

doi:10.1186/s12889-020-09039-z

Cited by 12 publications

(10 citation statements)

References 13 publications

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“…Further research is needed to identify the ecological variables that might modify the impact of RTS,S through these mechanisms. In Lilongwe, Malawi, proximity to wetlands, identified using satellite imagery, was found to be related to RTS,S/AS01e efficacy, possibly because there was rebound malaria in higher transmission intensity areas [ 37 ]. The environmental context of households must be analyzed in conjunction with household ecological variables such as ITN and IRS use as well as household socioeconomic context.…”

Section: Ecologymentioning

confidence: 99%

“…The environmental context of households must be analyzed in conjunction with household ecological variables such as ITN and IRS use as well as household socioeconomic context. Each participant’s household roof type (metal versus grass), which is a socioeconomic indicator, was measured in the Malawi phase III trial site but was not found to be related to vaccine efficacy [ 37 ]. However, a recent analysis from Kintampo, Ghana, found that vaccine efficacy was higher in high-SES households, partially determined by household construction materials [ 48 ].…”

Section: Ecologymentioning

confidence: 99%

“…Thus, those residing in certain ecologies experience higher rates of malaria than in others. Importantly, studies of phase II and III data have suggested potential differences in vaccine efficacy by transmission intensity, most suggesting efficacy to be higher in lower transmission intensity settings [32][33][34][35][36][37]. It is important to note that efficacy is a ratio measure and, thus, a vaccine with homogenous efficacy will have a greater absolute impact (in terms of cases averted) in high transmission settings.…”

Section: Ecologymentioning

confidence: 99%

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Impacts of Ecology, Parasite Antigenic Variation, and Human Genetics on RTS,S/AS01e Malaria Vaccine Efficacy

et al. 2021

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Purpose of Review Global malaria elimination has little chance of success without an effective vaccine. The first malaria vaccine, RTS,S/AS01e, demonstrated moderate efficacy against clinical malaria in phase III trials and is undergoing large-scale effectiveness trials in Africa. Importantly, the vaccine did not perform equally well between phase III study sites. Though reasons for the moderate efficacy and this variation are unclear, various mechanisms have been suggested. This review summarizes the recent literature on such mechanisms, with a focus on those involving landscape ecology, parasite antigenic variation, and human host genetic differences. Recent Findings Transmission intensity may have a role pre- and post-vaccination in modulating immune responses to the vaccine. Furthermore, malaria incidence may “rebound” in vaccinated populations living in high transmission intensity settings. There is growing evidence that both genetic variation in the parasite circumsporozoite protein and variation of human host genetic factors affect RTS,S vaccine efficacy. These genetic factors may be interacting in complex ways to produce variation in the natural and vaccine-induced immune responses that protect against malaria. Summary Due to the modest efficacy of RTS,S/AS01e, the combinations of factors (ecological, parasite, human host) impacting its effectiveness must be clearly understood, as this information will be critical for implementation policy and future vaccine designs.

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Section: Ecologymentioning

confidence: 99%

Section: Ecologymentioning

confidence: 99%

Section: Ecologymentioning

confidence: 99%

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Impacts of Ecology, Parasite Antigenic Variation, and Human Genetics on RTS,S/AS01e Malaria Vaccine Efficacy

et al. 2021

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“…The MVIP in Ghana commenced in May 2019, shortly after the launch of the vaccine in Malawi in April 2019 (Bell et al, 2020;Hogan et al, 2020). Alongside Ghana and Malawi, Kenya is also one of the chosen countries in SSA for the MVIP (Hogan et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Barriers and facilitators to nationwide implementation of the malaria vaccine in Ghana

Adeshina

Nyame

Milner

et al. 2022

Health Policy and Planning

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Interventions such as antimalarial drugs, bed nets and insecticides have helped curb the burden of malaria in the past decade, yet malaria remains a leading cause of morbidity and mortality in children below the age of five years. In 2019, Ghana, Malawi, and Kenya in sub-Saharan Africa (countries with moderate to high transmission areas of malaria and deaths) started piloting the RTS,S/AS01E malaria vaccine in selected regions. Using qualitative methods, this study examined the main factors (forces) that will influence or hinder the nationwide implementation of the malaria vaccine, if approved, in Ghana. We conducted in-depth interviews with 12 key individuals (national, research/academia, and program implementing partners) in the public health sector in Ghana in October 2018 to February 2019. Results were analyzed using Kurt Lewin’s force field analysis (FFA) to understand how organizations interact with their external environment in the delivery of health policies such as the implementation of the malaria vaccine. We found that the disease burden of malaria deaths in Ghana, efficacy of the vaccine, stakeholder involvement, and evidence for feasibility of vaccine delivery generated by the consortium of researchers (body of researchers) that can track the implementation were the driving forces to scale up the vaccine into routine health system. On the other hand, the needed logistics, funding, administration of the 4-dose vaccine and follow up were identified as potential barriers. The most influential force collectively highlighted by the respondents was the disease burden, and the most influential barrier was the logistics of delivering the vaccine. Our findings provide decision-makers with key barriers and facilitators to guide policy and decision-making for malaria control in Ghana and other similar settings in low middle-income countries.

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“…RTS,S, administered with AS01, is a liposome-based vaccine adjuvant containing monophosphorylate lipid A (MPLA) and is a recombinant antigen which was the first malaria vaccine to undergo pilot implementation, and currently vaccinates 360,000 children per year in Malawi, Ghana and Kenya [6,7]. However, clinical results have shown that the efficacy of RTS,S was ranging from 26% to 50% in infants and young children [8]. Therefore, research on malaria vaccines is continuing.…”

Section: Introductionmentioning

confidence: 99%

Alum Pickering Emulsion as Effective Adjuvant to Improve Malaria Vaccine Efficacy

Chen

Gao

et al. 2021

Vaccines

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Malaria is a life-threatening global epidemic disease and has caused more than 400,000 deaths in 2019. To control and prevent malaria, the development of a vaccine is a potential method. An effective malaria vaccine should either combine antigens from all stages of the malaria parasite’s life cycle, or epitopes of multiple key antigens due to the complexity of the Plasmodium parasite. Malaria’s random constructed antigen-1 (M.RCAg-1) is one of the recombinant vaccines, which was selected from a DNA library containing thousands of diverse multi-epitope chimeric antigen genes. Moreover, besides selecting an antigen, using an adjuvant is another important procedure for most vaccine development procedures. Freund’s adjuvant is considered an effective vaccine adjuvant for malaria vaccine, but it cannot be used in clinical settings because of its serious side effects. Traditional adjuvants, such as alum adjuvant, are limited by their unsatisfactory immune effects in malaria vaccines, hence there is an urgent need to develop a novel, safe and efficient adjuvant. In recent years, Pickering emulsions have attracted increasing attention as novel adjuvant. In contrast to classical emulsions, Pickering emulsions are stabilized by solid particles instead of surfactant, having pliability and lateral mobility. In this study, we selected aluminum hydroxide gel (termed as “alum”) as a stabilizer to prepare alum-stabilized Pickering emulsions (ALPE) as a malaria vaccine adjuvant. In addition, monophosphoryl lipid A (MPLA) as an immunostimulant was incorporated into the Pickering emulsion (ALMPE) to further enhance the immune response. In vitro tests showed that, compared with alum, ALPE and ALMPE showed higher antigen load rates and could be effectively endocytosed by J774a.1 cells. In vivo studies indicated that ALMPE could induce as high antibody titers as Freund’s adjuvant. The biocompatibility study also proved ALMPE with excellent biocompatibility. These results suggest that ALMPE is a potential adjuvant for a malaria vaccine.

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Environmental modifiers of RTS,S/AS01 malaria vaccine efficacy in Lilongwe, Malawi

Cited by 12 publications

References 13 publications

Impacts of Ecology, Parasite Antigenic Variation, and Human Genetics on RTS,S/AS01e Malaria Vaccine Efficacy

Impacts of Ecology, Parasite Antigenic Variation, and Human Genetics on RTS,S/AS01e Malaria Vaccine Efficacy

Barriers and facilitators to nationwide implementation of the malaria vaccine in Ghana

Alum Pickering Emulsion as Effective Adjuvant to Improve Malaria Vaccine Efficacy

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