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Pathogens & People: RSV vaccine a

challenge for scientists


By EDWARD McSWEEGAN, For The Capital
Published February 01, 2009

The cold and flu season is here so it seems an appropriate time to discuss another
"common cold" virus whose seasonal appearance may wander from mid-October
in some states to early July in others.

This errant pathogen is called the Respiratory Syncytial Virus or RSV. It belongs
to the same viral family as the measles and mumps viruses, but it behaves less
like them and more like the influenza virus. As with the flu virus, RSV's genetic
material is RNA (instead of DNA), it has a protective outer envelope and it comes
in two strains (A and B). And as with the flu virus, it also spreads rapidly from
person to person.

RSV usually causes a minor respiratory infection in adults. In very young


children, however, it is the most common cause of pneumonia and inflammation
of the airways (bronchiolitis). By age 3, almost every child in the U.S. has

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experienced a minor RSV infection. Yet each year, between 75,000 and 125,000
children are hospitalized with a serious RSV infection. What begins as a cough
with sneezing and a low-grade fever can progress to audible wheezing, cyanosis
(low oxygen in the blood) and apnea (interrupted breathing).

Hospital treatment tends to be supportive and may include oxygen and


mechanical ventilators for serious breathing difficulties. Bronchodilators such as
Albuterol have sometimes been used, and the anti-viral drug Ribavirin has been
tried in some studies, but its overall usefulness is unclear.

This is the problem with viral diseases: there are few good, specific drugs for
effective treatment and fewer available vaccines for prevention.

For RSV, the absence of effective drugs or a vaccine means it will continue to
cause significant morbidity and mortality, and the possibility of chronic
complications, among many pediatric patients. Children with underlying illnesses
and immune deficiencies may be especially susceptible to serious RSV infection
and lingering complications. For them, a kind of "instant immunity" is available
in the form of pre-made antibodies to the virus.

In 1996, the FDA licensed a monthly intravenous infusion of hyperimmune sera


for preterm infants at possible risk of RSV. A newer immune preparation called
''humanized IgG monoclonal antibody'' is available now and can be delivered as a
simple intramuscular injection.

Not surprisingly, RSV is a major cause of respiratory disease and death in the
developing world. India, for example, has mortality rates for acute respiratory
infections caused by flu, RSV and parainfluenza viruses that are 10 to 50 times
higher than in the West. In the U.S., poor rural and Native American populations
bear much of the burden of serious RSV infections.

Interestingly, part of the CDC's Arctic Investigations Program in Alaska is


specifically dedicated to RSV surveillance and prevention among the state's
native populations. The Alaska program has delivered anti-RSV monoclonal

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injections to high-risk infants, educational materials to tribal members and is
assessing candidate RSV vaccines for future clinical trials.

For many at-risk populations and patients, a vaccine would be an ideal means of
reducing disease, death and medical costs. Unfortunately, making a safe and
effective RSV vaccine has proven to be surprisingly difficult. The first such effort
began in the 1960s with a crude formalin-inactivated virus preparation. The
children who were vaccinated still contracted RSV and actually had more serious
RSV infections than unvaccinated children. That finding suggested to researchers
that normal host immune responses played a role in the pathogenesis of RSV
infections, and the vaccine had somehow enhanced or encouraged an overly
aggressive immune response. (A similar enhanced vaccine-immune response also
has been seen with another viral infection: dengue fever.)

Since then, RSV vaccine constructs have become more high-tech, consisting of
recombinant carrier viruses or purified viral proteins. Some of these - including
subunit vaccines made from the RSV F protein, and purified F, G and M proteins
- have been tested in small clinical trials. None has reached the stage of large-
scale trials yet, and it is likely to be many more years before a RSV vaccine is
available for at-risk children.

For more information about RSV see www.cdc.gov/rsv.

Dr. Edward McSweegan has a Ph.D. in microbiology and lives in Crofton. He


works on and writes about infectious disease issues. He may be contacted at
mcsweegan@nasw.org.

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