Sartorisu-Sowmya eBook - 14

DECIPHERING THE IMMUNE RESPONSE TO VIRAL INFECTION

lipopeptide ligand for TLR2/6 (that is, Pam2CSK4) and a class
C unmethylated 2'-deoxyribocytidine-phosphate-guanosine
(CpG) ligand for TLR9 (that is, ODN M362).
The investigators next pursued the biology of the effect.
"The combo (Pam2-ODN) induced production of reactive
oxygen species without reliance on type I interferon signaling.
Essentially, the lung epithelial cells were producing 'Clorox' to kill
pathogens," quipped Dickey.
The scientists also recently discovered the mechanism of
action, which presented another surprise. Dickey reported, "The
ODN in the mix binds a cytoplasmic DNA sensor that is required
for the rather magical effect in which all three players are
engaged to induce pathogen killing."
The PAM2- ODN therapeutic is currently in a Phase IIa
trial. " We are testing its ability to block bronchitis caused
by rhinovirus in a challenge study," Dickey said. However,
other uses include treating cancer patients undergoing
myeloablative chemotherapy, who are very susceptible
to pneumonia, as well as organ transplantation patients
and others on immunosuppressants. Dickey concluded
that "there are many strategies that could be developed,
now that we know combinations of innate ligands
delivered by aerosol to the lungs are capable of inducing
a high level of broad host resistance against a variety of
pathogens."
14 | GENengnews.com

MRNA VACCINES: THE BODY AS BIOREACTOR
Billions of people worldwide are at risk from endemic and newly
emerging tropical infectious diseases. Although traditional
vaccines have had an enormous impact on preventing
disease and saving lives, hurdles remain to more rapid vaccine
development and deployment.
Some believe that the introduction of mRNA vaccines could
usher in a new era in vaccinology. Although early reports of
successful use of in vitro transcribed mRNA in animals appeared
more than 30 years ago, only recently have major technological
innovations allowed mRNA to begin taking its place as a viable
therapeutic.
"Typical vaccines often utilize recombinant proteins, but
the need to produce and purify them are major hurdles,"
explained Jeroen Pollet, PhD, assistant professor of pediatrics
at the National School of Tropical Medicine at Baylor College
of Medicine in Houston. "Once a platform is developed, the
process can be streamlined. It is even conceivable to combine
mRNAs against different antigens to increase potency."
According to Pollet, mRNA vaccines offer some significant
advantages: "There is no risk of genomic integration. The
cellular immune response can be regulated both by nucleoside
modifications and delivery methods, and mRNA vaccines can be
produced by rapid, inexpensive, and scalable means."
Pollet and colleagues at Texas Children's Hospital Center
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