Background & Strategy

Background

Zika virus is an emerging mosquito-borne virus that was first identified in Uganda in 1947 in rhesus monkeys through a monitoring network of sylvatic yellow fever[1],[2].  The first human infection was reported in Nigeria in 1954[3].  Outbreaks of Zika virus disease have been recorded in Africa, the Americas, Asia and the Pacific, typically accompanied by mild illness.  The first large outbreak of disease caused by Zika infection was reported from the Island of Yap (Federated States of Micronesia) in 2007[4].  Between October 2013 and April 2014, French Polynesia experienced the largest Zika outbreak ever reported at that time[5].  More than 32,000 patients were suspected for Zika virus infection.  Between 2014 and 2015, Zika virus had spread to other Pacific islands, notably the Cook Islands and Easter Island (Chile).  In March 2015, Brazil reported the autochthonous transmission of Zika virus[6] and declared an unprecedented outbreak six months later[7] with preliminary estimates of 440,000 to 1.3 million cases of infection through December 2015[8].  More than 540.000 suspected cases and >198.000 confirmed cases have been reported up to January 2017[9].

 

Countries that have past or current evidence of Zika virus transmission, as of January 2016

Countries that have past or current evidence of Zika virus transmission, as of January 2016

(Source: European Centers for Disease Control and Prevention).

 

Zika virus is transmitted to people through the bite of an infected mosquito from the Aedes genus, mainly Aedes aegypti in tropical regions.  This is the same mosquito that transmits dengue, chikungunya and yellow fever.  Other modes of transmission such as blood transfusion are being investigated.

While mostly causing only mild illness, the virus has in recent outbreaks been associated with severe complications, such as Guillain-Barré syndrome and, when contracted during pregnancy, with microcephaly and other abnormalities of the central nervous system of the fetus[10],[11],[12].

In February 2016, the World Health Organization (WHO) has declared the recent outbreak of the Zika virus a Public Health Emergency of International Concern.  In November 2016, WHO indicated that Zika virus and associated consequences remain a significant public health challenge requiring intense action. 

In this context, in March 2016, experts gathered at WHO agreed that the development of a preventive vaccine is a major priority to respond to Zika epidemics in the future[13].  A first target product profile (TPP) for Zika vaccines was recently finalised and published jointly with UNICEF.[14],[15]

Strategy  

The development of a safe, effective and affordable vaccine for the prevention of Zika virus infections has become a global health priority for preventing the further spread of the virus.  To address this issue and allow for a fast track development, the ZIKAVAX consortium proposes to build upon one of the safest and most efficacious vaccines available, the live attenuated measles vaccine, as a delivery vector for Zika virus protective antigens to ensure the timely availability of a preventive vaccine whenever a new epidemic occurs. 

This delivery platform technology has demonstrated proof of principle in humans and a preclinical track record of rapid adaptability and effectiveness for a variety of pathogens.  Moreover, the manufacturing process for these measles vector-based vaccines has been developed to give higher yields and purity than the standard measles vaccine manufacturing process. 

The overall strategy of the ZIKAVAX project is to:

  1. Construct and characterise recombinant MV expressing Zika virus proteins as soluble secreted antigens
  2. Demonstrate preclinical immunogenicity and protective efficacy of the recombinant MV-Zika vaccine candidate(s) in a mouse and non-human primate (NHP) models of Zika virus infection
  3. Manufacture a good manufacturing practice (GMP) clinical lot of the MV-Zika vaccine candidate using a scalable platform technology
  4. Assess the safety and immunogenicity of the MV-Zika vaccine candidate in a phase I dose-escalation clinical trial.

[1] Gubler D et al. Flaviviruses. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, et al, eds.
Fields Virology, 5th edn. Philadelphia, PA: Lippincott Williams & Wilkins Publishers, 2007: 1155–227.

[2] Dick GWA et al, Trans R Soc Trop Med Hyg 1952; 46: 509–20

[3] Macnamara FN, Trans R Soc Trop Med Hyg 1954; 48: 139–45

[4] Duffy MR et al, N Engl J Med 2009; 360: 2536–43.

[5] Cao-Lormeau VM et al, Emerg Infect Dis 2013; 20: 1085–86.

[6] Zanluca C et al, . Mem Inst Oswaldo Cruz 2015; 110: 569–72.

[7] Dyer O, BMJ 2015; 351: h6983.

[8] European Centre for Disease Prevention and Control, De- cember 10, 2015 (http://ecdc.europa.eu/ en/publications/Publications/zika-virus-americas-association-with-microcephaly-rapid-risk-assessment.pdf).

[10] WHO. Guillain-Barré syndrome – El Salvador. Jan 21, 2016. http://www.who.int/csr/don/21-january-2016-gbs-el-salvador/en/ (accessed Feb 5, 2016).

[11] ECDC. Rapid risk assessment. Zika virus epidemic in the Americas: potential association with microcephaly and Guillain-Barré syndrome. Dec 10, 2015. http://ecdc.europa.eu/en/publications/ Publications/zika-virus-americas-association-with-microcephaly- rapid-risk-assessment.pdf (accessed Feb 5, 2016).

[12] Soares de Araújo J, Regis CT, Silva Gomes RG, et al. Microcephaly in northeast Brazil: a review of 16 208 births between 2012 and 2015. http://who.int/bulletin/online_first/16-170639.pdf?ua=1 (accessed Feb 8, 2016).

[14] Vannice KS, et al. Meeting Report: doi: 10.1016/j.vaccine.2016.10.034. [Epub ahead of print]