Immunogenicity, safety, and tolerability of the measles-vectored chikungunya virus vaccine MV-CHIK: a double-blind, randomised, placebo-controlled and active-controlled phase 2 trial

Reisinger, Emil C.; Tschismarov, Roland; Beubler, Eckhard; Wiedermann, Ursula; Firbas, Christa; Loebermann, Micha; Pfeiffer, Andrea; Muellner, M.; Tauber, Erich; Ramsauer, Katrin

doi:10.1016/s0140-6736(18)32488-7

Cited by 140 publications

(179 citation statements)

References 25 publications

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“…Moreover, pre-existing immunity to the measles vector did not affect the vaccine's immunogenicity. These data support the broader use of this platform for other emerging pathogens, such as Lassa fever [101].…”

Section: Measles Virus Vector Platformsupporting

confidence: 71%

Vaccine platforms for the prevention of Lassa fever

2019

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A B S T R A C TLassa fever is an acute viral haemorrhagic illness caused by Lassa virus (LASV), which is endemic throughout much of West Africa. The virus primarily circulates in the Mastomys natalensis reservoir and is transmitted to humans through contact with infectious rodents or their secretions; human-to-human transmission is documented as well. With the exception of Dengue fever, LASV has the highest human impact of any haemorrhagic fever virus. On-going outbreaks in Nigeria have resulted in unprecedented mortality. Consequently, the World Health Organization (WHO) has listed LASV as a high priority pathogen for the development of treatments and prophylactics. Currently, there are no licensed vaccines to protect against LASV infection. Although numerous candidates have demonstrated efficacy in animal models, to date, only a single candidate has advanced to clinical trials. Lassa fever vaccine development efforts have been hindered by the high cost of biocontainment requirements, the absence of established correlates of protection, and uncertainty regarding the extent to which animal models are predictive of vaccine efficacy in humans. This review briefly discusses the epidemiology and biology of LASV infection and highlights recent progress in vaccine development.

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Section: Measles Virus Vector Platformsupporting

confidence: 71%

Vaccine platforms for the prevention of Lassa fever

2019

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“…A Schwarz vaccine strain expressing Chikungunya virus (CHIKV) structural proteins has successfully completed phase II. Safety and immunogenicity were demonstrated, with up to 95.9% of patients achieving seroconversion [10]. This vaccine mediates expression of CHIKV virus-like particles.…”

Section: Introductionmentioning

confidence: 99%

Measles Vaccines Designed for Enhanced CD8+ T Cell Activation

Busch

Kubon

Mayer

et al. 2020

Viruses

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Priming and activation of CD8 + T cell responses is crucial to achieve anti-viral and anti-tumor immunity. Live attenuated measles vaccine strains have been used successfully for immunization for decades and are currently investigated in trials of oncolytic virotherapy. The available reverse genetics systems allow for insertion of additional genes, including heterologous antigens. Here, we designed recombinant measles vaccine vectors for priming and activation of antigen-specific CD8 + T cells. For proof-of-concept, we used cytotoxic T lymphocyte (CTL) lines specific for the melanoma-associated differentiation antigen tyrosinase-related protein-2 (TRP-2), or the model antigen chicken ovalbumin (OVA), respectively. We generated recombinant measles vaccine vectors with TRP-2 and OVA epitope cassette variants for expression of the full-length antigen or the respective immunodominant CD8 + epitope, with additional variants mediating secretion or proteasomal degradation of the epitope. We show that these recombinant measles virus vectors mediate varying levels of MHC class I (MHC-I)-restricted epitope presentation, leading to activation of cognate CTLs, as indicated by secretion of interferon-gamma (IFNγ) in vitro. Importantly, the recombinant OVA vaccines also mediate priming of naïve OT-I CD8 + T cells by dendritic cells. While all vaccine variants can prime and activate cognate T cells, IFNγ release was enhanced using a secreted epitope variant and a variant with epitope strings targeted to the proteasome. The principles presented in this study will facilitate the design of recombinant vaccines to elicit CD8 + responses against pathogens and tumor antigens.

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“…One attenuated CHIKV vaccine (181/clone 25) was developed and clinically evaluated (Levitt et al, 1986;McClain et al, 1998) but clinical trials were halted early when five treated subjects developed transient (< 24 h), mild arthralgia within the first 2 weeks of vaccination (Gorchakov et al, 2012). Recently, a liveattenuated vaccine (MV-CHIK), generated from the insertion of CHIKV structural proteins into measles vectored vaccine strain, showed positive results in a phase 2 clinical trial (Ramsauer et al, 2015;Reisinger et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Mutating chikungunya virus non‐structural protein produces potent live‐attenuated vaccine candidate

et al. 2019

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Currently, there are no commercially available live‐attenuated vaccines against chikungunya virus ( CHIKV ). Here, CHIKV s with mutations in non‐structural proteins (nsPs) were investigated for their suitability as attenuated CHIKV vaccines. R532H mutation in nsP1 caused reduced infectivity in mouse tail fibroblasts but an enhanced type‐I IFN response compared to WT ‐ CHIKV . Adult mice infected with this nsP‐mutant exhibited a mild joint phenotype with low‐level viremia that rapidly cleared. Mechanistically, ingenuity pathway analyses revealed a tilt in the anti‐inflammatory IL ‐10 versus pro‐inflammatory IL ‐1β and IL ‐18 balance during CHIKV nsP‐mutant infection that modified acute antiviral and cell signaling canonical pathways. Challenging CHIKV nsP‐mutant‐infected mice with WT ‐ CHIKV or the closely related O'nyong‐nyong virus resulted in no detectable viremia, observable joint inflammation, or damage. Challenged mice showed high antibody titers with efficient neutralizing capacity, indicative of immunological memory. Manipulating molecular processes that govern CHIKV replication could lead to plausible vaccine candidates against alphavirus infection.

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Immunogenicity, safety, and tolerability of the measles-vectored chikungunya virus vaccine MV-CHIK: a double-blind, randomised, placebo-controlled and active-controlled phase 2 trial

Cited by 140 publications

References 25 publications

Vaccine platforms for the prevention of Lassa fever

Vaccine platforms for the prevention of Lassa fever

Measles Vaccines Designed for Enhanced CD8+ T Cell Activation

Mutating chikungunya virus non‐structural protein produces potent live‐attenuated vaccine candidate

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