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Rescue and Characterization of Recombinant Virus from a New World Zika Virus Infectious Clone
Published on: June 7, 2017
An optimized messenger RNA vaccine candidate protects non-human primates from Zika virus infection
Brooke Bollman1, Naveen Nunna2, Kapil Bahl2
1Moderna, Inc., Cambridge, MA, USA. Brooke.Bollman@modernatx.com.
Abstract:
Zika virus (ZIKV), an arbovirus transmitted by mosquitoes, was identified as a cause of congenital disease during a major outbreak in the Americas in 2016. Vaccine design strategies relied on limited available isolate sequence information due to the rapid response necessary. The first-generation ZIKV mRNA vaccine, mRNA-1325, was initially generated and, as additional strain sequences became available, a second mRNA vaccine, mRNA-1893, was developed. Herein, we compared the immune responses following mRNA-1325 and mRNA-1893 vaccination and reported that mRNA-1893 generated comparable neutralizing antibody titers to mRNA-1325 at 1/20th of the dose and provided complete protection from ZIKV challenge in non-human primates. In-depth characterization of these vaccines indicated that the observed immunologic differences could be attributed to a single amino acid residue difference that compromised mRNA-1325 virus-like particle formation.
Insights
The second-generation Zika virus (ZIKV) mRNA vaccine, mRNA-1893, is more potent than the first-generation mRNA-1325 vaccine. mRNA-1893 provides complete protection in non-human primates at a lower dose, offering improved ZIKV vaccine development.
Area of Science:
- Virology and Immunology
- Vaccine Development
- Arbovirology
Background:
- Zika virus (ZIKV) emerged as a significant public health threat, causing congenital abnormalities during the 2016 Americas outbreak.
- Initial ZIKV vaccine development was hampered by limited sequence data, leading to the creation of first-generation mRNA vaccines.
- The first-generation ZIKV mRNA vaccine, mRNA-1325, was developed under urgent circumstances.
Purpose of the Study:
- To compare the immunogenicity and efficacy of two ZIKV mRNA vaccines: mRNA-1325 and mRNA-1893.
- To investigate the molecular basis for potential differences in immune responses elicited by the two vaccine candidates.
- To evaluate the protective potential of the second-generation vaccine against ZIKV challenge.
Main Methods:
- Comparative analysis of immune responses, including neutralizing antibody titers, following vaccination with mRNA-1325 and mRNA-1893.
- Assessment of vaccine efficacy through ZIKV challenge studies in non-human primate models.
- In-depth characterization of vaccine candidates to identify structural or functional differences, focusing on virus-like particle formation.
Main Results:
- mRNA-1893 demonstrated comparable neutralizing antibody titers to mRNA-1325 but at a significantly lower dose (1/20th).
- Vaccination with mRNA-1893 provided complete protection against ZIKV challenge in non-human primates.
- A single amino acid difference was identified as a key factor contributing to the immunologic disparities, specifically affecting mRNA-1325's virus-like particle formation.
Conclusions:
- The second-generation ZIKV mRNA vaccine, mRNA-1893, exhibits superior potency and efficacy compared to the first-generation mRNA-1325.
- mRNA-1893 represents a promising candidate for advanced ZIKV vaccine development due to its enhanced immunogenicity and protective capacity.
- Understanding the impact of specific molecular differences is crucial for optimizing future mRNA vaccine designs.
