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Respiratory Syncytial Virus
Preventing Respiratory Syncytial Virus Infection—Where Is the Vaccine?
a report by
Joseph B Domachowske, MD
Department of Pediatrics, State University of New York Upstate Medical University
Since 2005, several new vaccines have been approved by the US Food A Success Story
and Drug Administration (FDA). These additions to the universal The first attempt at preventing RSV disease using a passive immunization
childhood immunization schedule now include vaccines to protect strategy was the use of a polyclonal antibody preparation called
against rotavirus gastroenteritis, human papillomavirus infection, RSV-immunoglobulin intravenous (IGIV), marketed as RespiGam™.
meningococcal infection, and pertussis in adolescents and adults. While RSV-IGIV is derived from plasma obtained from selected human donors
the individual and public health benefits of these efforts are proven, with high-titer anti-RSV neutralizing activity. Although effective at
intuitive, and progressive, healthcare providers are left wondering why reducing the rate of severe RSV disease in some high-risk infants, a major
we still do not have a safe and effective respiratory syncytial virus (RSV) disadvantage was the need to administer the product as large-volume
vaccine. RSV disease is a prime target for vaccine development because infusions. A landmark study
3
showed that RSV-IGIV was effective in
RSV infection is ubiquitous. Nearly all affected children are infected preventing RSV hospitalizations and serious disease in premature infants
before their second birthday, and between 1 and 3% will require with or without chronic lung disease of prematurity, but a similar study
hospitalization. The primary risk factors for the development of serious carried out in infants with congenital heart disease
4
found no evidence to
RSV infection include prematurity, chronic lung disease, and support RSV-IGIV as safe in that high-risk population. With advances in
hemodynamically significant congenital heart disease. Secondary risk neutralizing monoclonal antibody technology, the production of the
factors include low birth-weight, multiple gestations (twins, etc.), young polyclonal RespiGam product was halted, and it is no longer
siblings in the same household, day-care attendance, and male gender. commercially available.
Term infants born with low cord blood RSV-neutralizing antibody titers
are known to develop RSV infection earlier in life, presumably due to the The successful development and implementation of palivizumab
lack of protective maternally transmitted antibodies. (Synagis
®
), a humanized monoclonal antibody that recognizes an RSV F-
protein epitope, offered significant advantages over RSV-IGIV. Palivizumab
RSV bronchiolitis is the single most common reason for infant hospitalization can be administered at one-fiftieth the dose of RSV-IGIV (15mg/kg) as
in the US with approximately 126,000 RSV-related admissions and 500 deaths monthly intramuscular injections instead of intravenous infusions.
occurring annually, costing our healthcare system in excess of $1 billion.
1
Palivizumab reduces RSV hospitalizations by 55% in premature infants with
Hospitalization is necessary for infants who develop hypoxemia secondary to or without chronic lung disease of prematurity, and by 45% in children
lower respiratory tract RSV infection. Young infants are also prone to develop with hemodynamically significant heart disease.
5,6
High-risk infants who
RSV-associated periodic breathing and apnea. Even when hospitalized, care is receive monthly injections of palivizumab during the RSV season are less
supportive as highly effective treatment interventions have yet to be likely to develop serious RSV infection, but there remains room for
identified. While infants with risk factors for serious RSV infection can be improvement. First, breakthrough infection is known to occur. Second, not
followed, and in many cases identified to receive RSV prophylaxis, many of the all high-risk infants receive prophylaxis. Third, the time from neonatal
infant hospitalizations still occur in previously healthy term infants. Preventing intensive care unit discharge of a high-risk infant to receipt of the first
RSV infection with a safe and effective vaccine would reduce infant morbidity dose, even during the RSV season, is, on average, 28 days. Finally, as the
and mortality and save healthcare dollars. product is a monoclonal antibody, protection is short-lived, resulting in only
short-term protection.
What is being done to prevent RSV disease in 2007? Can we expect to add
an RSV vaccine to our universal infant immunization schedule? Despite
Joseph B Domachowske, MD, is an Associate Professor of
decades of intense research, a safe and effective RSV vaccine that can be
Pediatrics, Microbiology, and Immunology at the State University
given to young infants has remained elusive. Perhaps the single most of New York’s Upstate Medical University in Syracuse. He is a
important concern is that vaccination may exacerbate naturally occurring
member of the American Academy of Pediatrics (AAP), the
Society for Pediatric Research (SPR), and the Infectious Disease
RSV infections, a phenomenon witnessed when an inactivated RSV vaccine
Society of America (IDSA). Dr Domachowske is the principal
was administered in clinical trials during the 1960s.
2
A second major obstacle investigator for several clinical and basic research studies that
to the development of an effective vaccine is that RSV infection itself, even
focus on identifying new intervention options for the treatment of
viral bronchiolitis. His research interests include the pathogenesis
in its most severe form, elicits only incomplete immunoprotection. A true
of and innate immune responses to respiratory syncytial virus.
surrogate of immunity simply does not exist. Moreover, a successful RSV
vaccine will need to protect against the two divergent RSV groups: A and B.
© T OUCH BRIEFINGS 2007
39
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