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51 years in of Chikungunya clinical vaccine development: A historical perspective.

ABSTRACT: Chikungunya fever (CHIKF) is a mosquito-borne disease caused by Chikungunya virus (CHIKV). This virus is considered a priority pathogen to the UK government, the US National Institute of Allergy and Infectious Diseases (NIAID) and the US military personnel, due to the potential of CHIKV to cause major outbreaks. Nearly all CHIKV infections are symptomatic, often incapacitating and patients experience severe joint pain and inflammation that can last for more than one year with 0.4-0.5% fatality rates. Mother-to-child transmission has also been described. Despite this re-emerging disease has been documented in more than 100 countries in Europe, Oceania, Africa, Asia, the Caribbean, South and North America, no licensed vaccine is yet available to prevent CHIKF. Nevertheless, various developments have entered phase I and II trials and are now viable options to fight this incapacitating disease. This review focuses on the development of CHIKV vaccines that have reached the stage of clinical trials since the late 1960s up until 2018.

SUBMITTER: Reyes-Sandoval A

PROVIDER: S-EPMC6816471 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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51 years in of Chikungunya clinical vaccine development: A historical perspective.

Reyes-Sandoval Arturo A

Human vaccines & immunotherapeutics 20190402 10

Chikungunya fever (CHIKF) is a mosquito-borne disease caused by Chikungunya virus (CHIKV). This virus is considered a priority pathogen to the UK government, the US National Institute of Allergy and Infectious Diseases (NIAID) and the US military personnel, due to the potential of CHIKV to cause major outbreaks. Nearly all CHIKV infections are symptomatic, often incapacitating and patients experience severe joint pain and inflammation that can last for more than one year with 0.4-0.5% fatality r ...[more]

PMID: 30735447

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Project description:BackgroundEpstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of research efforts to combat this major global health burden, there is no approved prophylactic vaccine against EBV. To facilitate the rational design and assessment of an effective vaccine, we systematically reviewed pre-clinical and clinical prophylactic EBV vaccine studies to determine the antigens, delivery platforms, and animal models used in these studies.MethodsWe searched Cochrane Library, ClinicalTrials.gov, Embase, PubMed, Scopus, Web of Science, WHO's Global Index Medicus, and Google Scholar from inception to June 20, 2020, for EBV prophylactic vaccine studies focused on humoral immunity.ResultsThe search yielded 5,614 unique studies. 36 pre-clinical and 4 clinical studies were included in the analysis after screening against the exclusion criteria. In pre-clinical studies, gp350 was the most commonly used immunogen (33 studies), vaccines were most commonly delivered as monomeric proteins (12 studies), and mice were the most used animal model to test immunogenicity (15 studies). According to an adaptation of the CAMARADES checklist, 4 pre-clinical studies were rated as very high, 5 as high, 13 as moderate quality, 11 as poor, and 3 as very poor. In clinical studies, gp350 was the sole vaccine antigen, delivered in a vaccinia platform (1 study) or as a monomeric protein (3 studies). The present study was registered in PROSPERO (CRD42020198440).ConclusionsFour major obstacles have prevented the development of an effective prophylactic EBV vaccine: undefined correlates of immune protection, lack of knowledge regarding the ideal EBV antigen(s) for vaccination, lack of an appropriate animal model to test vaccine efficacy, and lack of knowledge regarding the ideal vaccine delivery platform. Our analysis supports a multivalent antigenic approach including two or more of the five main glycoproteins involved in viral entry (gp350, gB, gH/gL, gp42) and a multimeric approach to present these antigens. We anticipate that the application of two underused challenge models, rhesus macaques susceptible to rhesus lymphocryptovirus (an EBV homolog) and common marmosets, will permit the establishment of in vivo correlates of immune protection and attainment of more generalizable data.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198440, identifier PROSPERO I.D. CRD4202019844.

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51 years in of Chikungunya clinical vaccine development: A historical perspective.

Publications

51 years in of Chikungunya clinical vaccine development: A historical perspective.

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