Making vaccines against RSV ( respiratory syncytial virus ) has been a minefield for 50 years, but scientists believe they have found the right balance.
Researchers from Emory University School of Medicine and Atlanta Children's Healthcare Group reported: "They have designed a version of RSV that is highly attenuated -- weakening its ability to cause disease, but with the ability to induce protective antibodies. Used as a vaccine, this engineered virus can protect mice and cotton rats from RSV infection.
results are scheduled for December 21 in "Nature Published in the journal Communications. "Our paper shows that it is possible to attenuate RSV without losing any immunogenicity." This is a promising live attenuated vaccine candidate that deserves further clinical research. "The next step for this vaccine is to produce clinical-grade batches and conduct a Phase 1 study of infant safety and immunogenicity," said
Moore. l0RSV is the leading cause of death from pneumonia in children worldwide and one of the leading causes of hospitalization in American infants. Most children in the United States are infected in the first year of their lives.
Even so, there is no vaccine for RSV. In the 1960s, an attempt was made to develop RSV vaccines through chemical inactivated viruses, such as in standard influenza vaccines, with back burning. Exposure to this vaccine actually makes natural RSV infection worse in infants. Recently, ht in older people Clinical trials of ml3 protein RSV vaccine show disappointing results.
has produced several successful vaccines against other viruses such as measles , polio and mumps .
Moore says, “It is a challenge to achieve this balance”. Attenuation of RSV by passage is not satisfactory, It turns out that for RSV, the natural virus itself does not induce a lot of immunity.
Instead, Moore and his colleagues designed RSV to enhance the production of key proteins called F (fusion). F is crucial for the ability of RSV to enter cells and is a target for several vaccines in development. By mutations in the genes encoding F, the researchers also made the virus more thermally stable, which contributes to vaccine production and distribution.
Meanwhile, the researchers deleted or weakened several other viral genes, promoting infection and suppressing the immune system. One such measurement is produced by modified viruses called OE4 stimulated high levels of antibodies.
Moore and his team used the codon de-optimized process to rewritten several viral genes in the OE4 strain, which made it unlikely that the redesigned virus would mutate back to its original form.
When examined by electron microscopy OE4 virions look similar to standard RSV virions, except that OE4 has higher levels of immunogenic form of F protein and lower levels of another protein called G.
OE4 vaccination completely protects mice and cotton rats from subsequent infection of standard form RSV. OE4 does not cause enhanced lung disease in cotton rats compared to chemically inactivated RSV vaccines.
Christopher, assistant professor of biology at Butler University Dr. Stobart and lecturer Dr. Christina Rostad are co-first authors of the paper. Cotton rat research was conducted at Baylor College of Medicine and Sigmovir Biosystems. (Xiu Yi Xiaowei 203658)
