A preclinical proof-of-concept study indicated that vaccines designed for the prevention of Zika Virus (ZIKV), using a self-amplifying RNA (SAM) platform delivered by cationic nacemulsion (CNE), can be use used a rapid response for ZIKV.
Research for this study was performed under a Cooperative Research and Development agreement between the National Institute of Allergy and Infectious Diseases (NIAID) and Glaxo Smith Kline (GSK) Biologicals. ZIKV can cause microcephaly in newborns and Guillan-Barre syndrome in adults and as of now has no available treatments or vaccines.
Vaccine candidates within the study demonstrated potent neutralizing antibody responses to ZIKV in mice and nonhuman primates, with one vaccine providing complete protection against the infection in nonhuman primates.
SAM technology is an RNA-based vaccine platform that uses 9-kbp SAM derived from an alphavirus genome. This type of vaccine can be produced rapidly through in vitro transcription. With SAM technology, there is a large amount of subgenomic RNA in situ which leads to a high expression of vaccine antigen levels, and the presence of double-stranded RNA which activates interferon pathways with a self-adjuvating effect.
As the RNA is generated in a cell-free in vitro system and is without potential cellular contaminants, it is suitable for rapid scale-up and can be used in response to an epidemic such as ZIKV. CNE, which the SAM vaccine is delivered through, can be stockpiled separately from the RNA for later use.
In February 2016, the World Health Organization (WHO) declared ZIKV a Public Health Emergency of International Concern following the spread of the infection through the Americas and Caribbean, specifically Brazil, Columbia, El Salvador, and Jamaica.
ZIKV also is predicted to continue to circulate and cause sporadic outbreaks, according to the WHO. Women, particularly women who are pregnant or may become pregnant are seen as the most in need of vaccines against ZIKV as the infection can have transmission to a fetus with major effects such as microcephaly.
The preclinical proof of concept study further indicated that SAM technology can be used for the rapid development of vaccine candidates. The properties of drug substances and the manufacturing of vaccines of this nature are the same for every antigen which can speed up process development and movement through the regulatory pathway. Antibody responses to vector structural proteins can also be circumvented due to the synthetic delivery of this technology, while antigen-specific immune responses can still be seen.