20 February 2018. A vaccine using synthetic RNA, with protein instructions transcribed from one’s genetic code, is shown in tests with lab animals to protect against infections from cytomegalovirus, a virus affecting infants and transplant recipients. Results of the study conducted by researchers with the biotechnology company Moderna Therapeutics in Cambridge, Massachusetts, appear in the 15 February issue of the journal Vaccine.
Cytomegalovirus, or CMV, is a virus in the herpes family found in large percentages of people, but adversely affecting smaller numbers of individuals. Centers for Disease Control and Prevention says nearly 1 in 3 children by age 5, and more than half of adults in the U.S. by age 40 are infected with CMV. In people with healthy immune systems, CMV does not cause illness, but in people with weakened immune systems, CMV infections can have serious consequences. Among those at risk are fetuses and newborns, who can develop congenital CMV, with symptoms including deafness, vision loss, and microcephaly like infants infected with the Zika virus. CMV is also the most frequent viral disease in transplant patients, but no vaccines protecting against CMV are yet approved.
Moderna develops therapeutic proteins with a technology that synthesizes messenger RNA, a nucleic acid with the genetic code from DNA used by cells to produce the amino acids in proteins for cellular functions. Moderna manipulates the coding region in the messenger RNA chemistry to provide instructions for cells to produce proteins with specific therapeutic properties. Those coding instructions are contained in a standard package that appears in most cases like natural RNA to avoid triggering an immune response, and reach the desired cells where the therapeutic protein is needed.
For protective vaccines, Moderna delivers messenger RNA with instructions for cells to produce proteins with enough resemblance to viruses to generate an immune response, but still safe for the recipient. In this case the company’s candidate vaccine, code-named mRNA-1647, is designed to produce glycoproteins — proteins with carbohydrates attached — in cells with characteristics of CMV like those found on the virus’s exterior. The vaccine also produces a complex of 5 proteins associated with CMV’s entry through skin and blood vessel cells.
Moderna tested mRNA-1647 in lab mice and monkeys, with the vaccine formulated into lipid, or natural body oil, nanoscale particles. The results show the vaccine produced in both mice and monkeys increases concentrations of antibodies, as measured by titers in their blood, that protect against CMV infections. In addition, the higher concentrations of antibodies remain in the animals for several months.
The company is also producing an associated vaccine that generates stronger responses with T-cells, a type of white blood cell in the immune system. This vaccine, also formulated as lipid nanoscale particles, seeks to active a protein known as pp65, also associated with CMV infections, and administered with the glycoprotein vaccine. In tests with lab mice, the combined vaccines produce higher concentrations of antibodies, but also generate strong T-cell responses.
While the paper gives results from a preclinical study of CMV vaccines, Moderna is already testing mRNA-1647 in an early-stage clinical trial. That study is looking primarily at the vaccine’s safety and immune responses against a placebo, among 209 healthy individuals at 3 sites in the U.S.
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