Results published in Microbiology Spectrum by researchers from the US demonstrate that their Zika vaccine technology is safe and effective in preclinical mouse models. As it stands there are no approved vaccines or alternative treatments for virus, but these results indicate that there may be hope on the horizon for a responsive and effective vaccine.
The article describes Zika virus (ZIKV) as a mosquito-borne human pathogen that “causes dire congenital brain developmental abnormalities in children of infected mothers”. The authors refer to the 2015/16 outbreak of ZIKV, which attracted “global attention” after it caused “dire teratogenic effects”. These included microcephaly and foetal mortality. Consequently, “intense research efforts” have continued, although to “little avail”.
The introduction explores how the “error-prone nature of RNA viral genome replication tends to promote evolution of novel viral strains”. Thus, the aim of this investigation was to develop a “replication-deficient ZIKV vector-based candidate”.
The finer details
The researchers, based at the University of California, Los Angeles (UCLA), described “generating a ZIKV vector containing only the nonstructural (NS) 5’-untranslated (UTR)-NS-3′ UTR sequences, with the structural proteins capsid (C), precursor membrane (prM), and envelop (E) (CprME) used as a packaging system.” They packaged replication-deficient Zika vaccine particles into human producer cells and “verified antigen expression” in vitro. In vivo studies concluded that after neonatal mice inoculation the candidate (ZVAX) was safe and “did not produce and replication-competent revertant viruses”.
Following successful immunisation of adult, non-pregnant mice, in which ZVAX limited viral replication, they evaluated the safety and efficacy in pregnant mice. It was “shown to provide efficient maternal and foetal protection” against the disease. Mass cytometry analysis demonstrated that these animals had “high levels of splenic CD8+ T cells and effector memory T cell responses with reduced proinflammatory cell responses”.
They also explored humoral immunity, potentially induced by “viral proteins present in ZVAX virions”. Finding “no significant difference” in neutralising antibody titer between vaccinated and unvaccinated animals, they inferred that “cellular immunity plays a major role in ZVAX-mediated protection”.
“In conclusion, we demonstrated ZVAX as an effective inducer of protective immunity against ZIKV, which can be further evaluated for potential prophylactic application in humans.”
Preventing future pandemics
Although it has been several years since the previous outbreak devastated the Americas, the average time between periods of severe viral spread is 7 years, so experts are on the lookout for emerging signs but also protective measures. Alongside this cyclical timeline is the danger caused by climate change. Increased habitat spread for mosquitoes like the Aedes aegypti increases the risk for more people.
To hear more about preparing for future pandemics at the World Vaccine Congress in Europe 2022 click here for tickets.