mRNA-1893 Zika Vaccine

Moderna's mRNA-1893 vaccine candidate contains an mRNA sequence encoding for the structural proteins of the Zika virus. It is designed to cause cells to secrete virus-like particles, mimicking the cell's response after a natural infection. Preclinical data published in the Journal of Infectious Diseases have shown that vaccination with mRNA-1893 protected mice against Zika virus transmission during pregnancy.

On August 19, 2019, Moderna, Inc. announced that the U.S. Food and Drug Administration (FDA) had granted Fast Track Designation for its investigational mRNA-189. It is currently being evaluated in a Phase 1 study to prevent Zika virus infection in healthy adults. This project has been funded in whole or in part with Federal funds from the Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority (BARDA), under Contract No. HHSO100201600029C.

As of July 12, 2022, the phase 1 study (mRNA-1893-P201) is active in Puerto Rico, with a completion date scheduled for April 26, 2024. On August 3, 2022, Moderna confirmed that the mRNA-1893 Phase 2 study was ongoing.

The Lancet Infectious Disease published on January 19, 2023: Promising efforts to develop an mRNA vaccine against Zika. These findings support the continued development of mRNA-1893 against the Zika virus, which was well tolerated at all evaluated dose levels and induced strong Zika virus-specific serum nAb responses after two doses, regardless of baseline flavivirus serostatus. On April 20, 2023, the journal NPJ Vaccines published - 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. These findings support the continued development of mRNA-1893 against Zika virus.

Headquartered in Cambridge, Mass., Moderna (Nasdaq: MRNA) currently has strategic alliances for development programs.

mRNA Technology

Recognizing the broad potential of mRNA science, Moderna set out to create an mRNA technology platform that functions very much like an operating system on a computer. It is designed to plug and play interchangeably with different programs. Generally, the only thing that changes from one potential mRNA medicine to another is the coding region – the actual genetic code that instructs ribosomes to make protein. Utilizing these instruction sets gives the investigational mRNA medicines a software-like quality. Moderna also can combine different mRNA sequences encoding for various proteins in a single mRNA investigational medicine.

mRNA-1893 Vaccine Indication

Zika virus is the first and only flaviviral disease the WHO (2016) declared a public health emergency because of devastating congenital disabilities following maternal infection. mRNA-1893 is indicated for avoiding transmission of the Zika disease from a mother to an unborn child.

mRNA-1893 Vaccine Dosage

Interim Phase 1 Data - All four cohorts (10 µg, 30 µg, 100 µg, 250 µg) of the Phase 1 study of mRNA-1893 have been dosed. An interim study analysis reports safety and immunogenicity data from the ten µg and 30 µg cohorts. In addition, neutralizing antibody titers were assessed using the Plaque Reduction Neutralization Test (PRNT50) and microneutralization assays (M.N.), which provide equivalent guidance for interpreting the neutralizing immune response.

mRNA-1893 Vaccine News

May 4, 2022 - Moderna confirmed the Phase 2 study of mRNA-1893 is ongoing in the U.S. and Puerto Rico and is being developed in collaboration with BARDA.

November 10, 2021 - The Hindustan Times reported that ZIKA virus cases had reached over 100 cases. Of the 105 positive cases, 17 are now negative.

November 4, 2021 - Moderna announced that its phase 2 study of mRNA-1893 is ongoing in the U.S. and Puerto Rico. mRNA-1893 is being developed in collaboration with BARDA. 

April 14, 2020 - The first interim analysis of the Phase 1 study shows that ten µg and 30 µg dose levels seroconverted 94% and 100% of seronegative participants, respectively, and effectively boosted seropositive participants; both dose levels were generally well-tolerated.

August 19, 2019 - Moderna Inc. announced that the Food and Drug Administration had approved its potential vaccine for the Zika virus for a fast track to approval. Fast Track is designed to facilitate the development and expedite the review of therapies and vaccines for serious conditions and to fill an unmet medical need. In addition, programs with Fast Track designation may benefit from early and frequent communication with the FD and a rolling marketing application submission. 

mRNA-1893 Vaccine Clinical Trials

mRNA-1893 Zika vaccine is currently being studied in two clinical trials. These were descriptive studies, with no formal hypothesis testing in either trial. Both trials are registered with ClinicalTrials.gov, NCT03014089 (mRNA-1325 trial) and NCT04064905 (mRNA-1893 trial).

Findings: The mRNA-1325 trial was done from Dec 14, 2016, to Aug 16, 2018. Ninety participants were enrolled: 53 (59%) participants were women, and 37 (41%) were men, 84 (93%) were White, and 74 (82%) were not Hispanic or Latino. All three dose levels of mRNA-1325 (10, 25, and 100 μg) were generally well tolerated, but the vaccine elicited poor Zika virus-specific nAb responses. At 28 days after dose two, geometric mean titres (GMTs) were highest for mRNA-1325 10 μg (10·3 [95% CI 5·9–18·2]). The mRNA-1893 trial was done from July 23, 2019, to March 22, 2021. One hundred twenty participants (70 [58%] women and 50 [42%] men) were enrolled, most participants were White (89 [74%]) and not Hispanic or Latino (91 [76%]). In the mRNA-1893 trial, solicited adverse reactions in participants who received a vaccine were mainly grade 1 or 2 and occurred more frequently at higher dose levels and after dose two. No participants withdrew due to an unsolicited treatment-emergent adverse event, and most of these events were not treatment-related. On day 57, all evaluated mRNA-1893 dose levels induced robust Zika virus-specific nAb responses, independent of flavivirus serostatus, that persisted until month 13. At day 57 in participants who were flavivirus seronegative, plaque reduction neutralization titre test nAb GMTs were highest for mRNA-1893 100 μg (454·2 [330·0–619·6]); in participants who were flavivirus seropositive, GMTs were highest for mRNA-1893 10 μg (224·1 [43·5–1153·5]) and mRNA-1893 100 μg (190·5 [19·2–1887·2]).