Scientists funded by the National Institutes
of Health have developed an investigational vaccine that protected
cynomolgus macaques against four types of hemorrhagic fever viruses
endemic to overlapping regions in Africa. The University of Texas
Medical Branch in Galveston and Profectus BioSciences of New York are
developing and testing the candidate quadrivalent VesiculoVax vaccine,
with support from NIH's National Institute of Allergy and Infectious
Diseases (NIAID) and Redeemer's University in Nigeria.
The newly published study in the Journal of Clinical Investigation
describes how the vaccine was created using a live-attenuated
(weakened) vesicular stomatitis virus to deliver proteins that elicit
protective immune responses. The proteins are from Ebola virus (Kikwit
strain), Sudan virus (Boniface strain, which also causes Ebola virus
disease), Marburg virus (Angola strain) and Lassa virus (Josiah strain).
There are no licensed vaccines to provide protection from any of those
viruses -- all of which can cause severe disease and death -- although
the European Medicines Agency has recommended licensing a VSV-Ebola
vaccine.
Importantly, the monkeys infected in the study were exposed to
different strains of Sudan virus (Gulu) and Lassa virus (0043/LV/14)
than those in the candidate vaccine to help the researchers determine
whether the vaccine would be cross-protective. Lassa 0043/LV/14 is
circulating in an outbreak in Nigeria that began in 2018. Previous
studies indicate that the investigational Ebola virus (Kikwit) vaccine
will protect against other strains of Ebola virus.
The scientists inoculated 20 macaques with a primary and booster dose
of quadrivalent VesiculoVax. The animals had five blood draws to check
for an immune response, including on the day of initial vaccination and
on days 10 and 28, then on day 56 when they received a booster
inoculation, and again on day 66. On day 84 scientists infected the
macaques with the four different hemorrhagic fever viruses and monitored
them to day 112.
Twelve additional macaques in the study who were infected with the
four viruses but not vaccinated all became sick, but none of the
vaccinated animals did. Only one of the 20 vaccinated animals had any of
the four hemorrhagic fever viruses detectible (Lassa) following the
study.
The scientists state that the addition of the Lassa virus component
to their multivalent vaccine is an exciting research advance as they
already had developed an investigational trivalent vaccine that provided
protection against Ebola, Sudan and Marburg viruses. The researchers
now plan further vaccine tests against other strains of Lassa virus, and
they want to further evaluate whether a single-dose quadrivalent
vaccine appears safe and effective.
Journal Reference:
- Robert W. Cross, Rong Xu, Demetrius Matassov, Stefan Hamm, Theresa E. Latham, Cheryl S. Gerardi, Rebecca M. Nowak, Joan B. Geisbert, Ayuko Ota-Setlik, Krystle N. Agans, Amara Luckay, Susan E. Witko, Lena Soukieh, Daniel J. Deer, Chad E. Mire, Heinz Feldmann, Christian Happi, Karla A. Fenton, John H. Eldridge, Thomas W. Geisbert. Quadrivalent Vesiculovax vaccine protects nonhuman primates from viral-induced hemorrhagic fever and death. Journal of Clinical Investigation, 2019; DOI: 10.1172/JCI131958
Courtesy: ScienceDaily
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