Vaccines for emerging infectious diseases: Lessons from MERS coronavirus and Zika virus

Figures & data

Table 1. Global viral epidemics since in the 21^st century.

Pathogen	Year of onset	Mortality rate	Mode of Transmission	Unique aspects
SARS-CoV	2002	10%	Zoonotic, person to person	Palm civets and Gambian rats served as reservoirs
Influenza H5N1	2003	60%	Zoonotic, person to person	Chickens and fowl serve as reservoir
Influenza H1N1	2009	0.02%	Person to person	Obesity adults as novel risk group
Influenza N3N2	2010	Ongoing	Person to person	Middle age adults as novel risk group
MERS-CoV	2012	38%	Zoonotic, person to person, droplet	Camels serve as reservoir
Influenza H7N9	2013	29%	Person to person
Chikungunya	2013 ^1	Rare	Arboviral	New outbreak in Americas
Ebola virus	2014 ^1	39%	Person to person	Worldwide dissemination of infected HCWs
Zika virus	2015 ^1	Rare	Arboviral	Microcephaly and other congenital defects

Abbreviations: HCW, healthcare worker; MERS-CoV, Middle East Respiratory Syndrome coronavirus; SARS-Cov, Severe Acute Respiratory Syndrome coronavirus.

¹ Outbreaks of chikungunya virus and Zika virus are those that were documented in the Americas, the outbreak of Ebola virus was restricted to West Africa.

Table 2. MERS-CoV vaccines: Phase I clinical trials and relevant pre-clinical references.

Vaccine	Sponsor	N	Type ^1	Location	Designation ^2	Entered into CTG ^3	Study opened	Reference
DNA plasmid
GLS-5300 ^4	WRAIR / GeneOne	75	OL, DR	MD ^5	NCT02670187	27 Jan 2016	Jan 2016	^36

¹ Study type: OL, open label; DR, dose ranging; PC, placebo-controlled; DB, double-blind.

² Clinical Trials Gov designation.

³ Date entered into Clinical Trials Gov.

⁴ GLS-5300 is being co-developed by GeneOne Life Science, Inc. and Inovio Pharmaceuticals, Inc.

⁵ The indicated studies have completed enrollment. Abbreviations: MD, Maryland.

Table 3. Zika virus vaccines: published pre-clinical studies and Phase I clinical trials.

Vaccine	Sponsor	N	Type ^1	Location	Designation ^2	Entered into CTG ^3	Study opened	Reference
DNA plasmid
GLS-5700	GeneOne	40	OL, DR	PA, FL, Que ^6	NCT02809443	20 Jun 2016	Jun 2016	^144
	GeneOne	160	PC, DB	PR ^7	NCT02887482	24 Aug 2016	Aug 2016
VRC-ZKADNA085-00-VP (VRC5288) ^4	NIAID	80	OL	GA, MD ^6	NCT02840487	19 Jul 2016	Aug 2016	^140,141,143
VRC-ZKADNA909-00-VP (VRC5283) ^4	NIAID	50	OL	MD ^7	NCT02996461	16 Dec 2016	Dec 2016	^140,141,143
mRNA
mRNA-1325	Moderna	90	OL, DR	CA, FL, IL ^7	NCT03014089	5 Jan 2017	Jan 2017	^146
PIV
ZPIV ^5	Beth Israel	48	DR, PC, DB	MA ^7	NCT02937233	12 Oct 2016	Oct 2016	^140,143
	NIAID	75	OL, DR	MO ^7	NCT02952833	13 Oct 2016	Oct 2016
	NIAID	90	OL	MD ^7	NCT02963909	10 Nov 2016	Nov 2016
	NIAID	90	DR, PC, DB	PR ^7	NCT03008122	15 Dec 2016	Dec 2016
Viral Vectored - MV
MV-ZIKA	Themis	48	DR, PC, DB	Austria ^7	NCT02996890	15 Dec 2016	Apr 2017

¹ Study type: OL, open label; DR, dose ranging; PC, placebo-controlled; DB, double-blind.

² Clinical Trials Gov designation.

³ Date entered into Clinical Trials Gov.

⁴ VRC5283 is a chimeric vaccine expressing JEV prM region that precedes the entire wild-type Zika virus envelope; VRC5288 is a chimeric vaccine that includes the JEV prM region preceding the first 98 amino acids of the Zika virus envelope and the stem and transmembrane regions from JEV.

⁵ For clinical trial NCT02963909 ZPIV is either given alone with alum or with Japanese encephalitis virus (JEV) vaccine Ixiaro (inactivated) or with Yellow Fever virus (YFV) vaccine YF-Vax (live virus vaccine that includes strain 17D. For trials NCT03008122 and NCT02952833.

ZPIV is administered with alum, whereas for trial NCT02937233 ZPIV is given without alum adjuvant.

⁶ The indicated studies have completed enrollment. Abbreviations: PA, Pennsylvania; FL, Florida; Que, Quebec City; GA, Georgia; MD, Maryland. GLS-5700 is being co-developed by GeneOne Life Science Inc. and Inovio Pharmaceuticals Inc.

⁷ The indicated studies have ongoing enrollment at the time of writing. Abbreviations: PR, Puerto Rico; CA, California; IL, Illinois; MA, Massachusetts; MO, Missouri.

Muthumani K, Falzarano D, Reuschel EL, Tingey C, Flingai S, Villareal DO, Wise M, Patel A, Izmirly A, Aljuaid A, et al. A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Sci Transl Med. 2015;7(301):301ra132. doi:10.1126/scitranslmed.aac7462. PMID:26290414

 PubMed Web of Science ®Google Scholar

Muthumani K, Griffin BD, Agarwal S, Kudchodkar S, Reuschel EL, Choi H, Kraynyak K, Duperret EK, Keaton AA, Chung C. In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunization with a prMEnv DNA vaccine. NPJ Vaccines. 2016;1:16021. doi:10.1038/npjvaccines.2016.21

 PubMed Web of Science ®Google Scholar

Richner JM, Himansu S, Dowd KA, Butler SL, Salazar V, Fox JM, Julander JG, Tang WW, Shresta S, Pierson TC, et al. Modified mRNA vaccines protect against Zika virus infection. Cell. 2017;168(6):1114-25. doi:10.1016/j.cell.2017.02.017. PMID:28222903

 PubMed Web of Science ®Google Scholar