Live-attenuated vaccine highly effective during influenza season

Protection provided by the live-attenuated vaccine may have been attributed to combination of both innate and adaptive immunity.

Issue: October 2007

Although the 2003-2004 influenza season unexpectedly arrived early and most children received only one dose of either the live-attenuated influenza vaccine or the inactivated influenza vaccine, the one-dose live-attenuated vaccine proved to be effective in protecting against influenza in this population.

“These results were surprising because for the first time, we were vaccinating through the influenza season and we only gave a single dose of both types of vaccines to the great majority of our children. We also had a major circulating virus, which was a drifted virus from the vaccine. Despite this, we were still able to demonstrate protection against influenza in children who received the live-attenuated influenza vaccine,” Pedro A. Piedra, MD, professor in the department of molecular virology and microbiology and pediatrics at the Baylor College of Medicine, told Infectious Diseases in Children.

“Another important finding is that we saw protection almost from the time the children were vaccinated; the vaccine appeared to be causing a non-specific protection against the influenza virus that was circulating in the environment at that time. This is consistent with protection provided by innate [immunity].”

Community-based study

In an open-label, nonrandomized, community-based study supported by the National Institutes of Health, the researchers compared influenza-positive medically-attended febrile respiratory illness and medically-attended acute respiratory illness in vaccinated children aged 5 to 18 years in intervention communities with age-eligible, non-participant children in the intervention and comparison communities.

The communities in central Texas were chosen based upon similar demographics. The relative closeness of their cities ensured similar influenza outbreaks and similar circulating influenza strains; all of the participants’ communities were served by large multispecialty clinics of the Scott and White Clinic (a major health care provider for these communities).

All participants received a single dose of an FDA-approved nasal-spray (LAIV-T, Flumist, MedImmune) or intramuscular injection influenza vaccine (IIV-T) at baseline; a second dose of the vaccine was offered four to six weeks following the first dose to children aged younger than 9 who received the vaccine for the first time.

Healthy children in the intervention group were offered LAIV-T and children at high risk for influenza were offered the IIV-T vaccine.

Results indicated that the participants who received the LAIV-T vaccine had a 37.3% protection rate (P<.05) against influenza-positive medically-attended febrile respiratory illness and a 50% protection rate against medically-attended pneumonia and influenza illness.

The LAIV-T vaccinated group had a similar protection rate against influenza within 14 days of vaccination compared with more than 14 days following vaccination (10 out of 25 vs. nine out of 30).

“We also found a herd protection in children aged 5 to 11 years. This effect was also seen in adults aged 35 to 44 years, but the major benefit was found in children,” Piedra said.

Vaccine effectiveness was most evident among children aged 5 to 9, with an 80% effectiveness against pneumonia and influenza medically-attended illness.

The researchers found that one dose of IIV-T was not associated with a significant reduction in medically-attended pneumonia and influenza illness.

According to the researchers, this may be due to the following reasons:

Most of the children were aged younger than 9 and had not received vaccination with the influenza vaccine prior to the study. Therefore, they only received one-dose of IIV-T during the outbreak.
IIV-T was associated with modest heterotypic protective antibody response to the variant circulating H3N2 virus.
Medically-attended acute respiratory illness, pneumonia and influenza illness during the outbreak were not sufficiently specified definitions for influenza.
The number of children in the intervention group who never received vaccination was not an adequate comparison to the group who received vaccination with IIV-T.

“Our ongoing community-based influenza vaccination program of children to control epidemic influenza provided us the opportunity to assess the effectiveness of LAIV-T and IIV-T when administered during an influenza outbreak,” the researchers wrote.

“There are supportive data that suggest that one dose of the LAIV-T vaccine will provide a good level of protection, but the two-dose regimen works best for the IIV-T vaccine in young children who receive the influenza vaccine for the first time,” Piedra said. “LAIV-T was very well-tolerated throughout the entire influenza outbreak, which is very important because not only do we want to see the benefit, but we want to ensure vaccine safety.”

“In future years, we will need to continue to evaluate for bias in estimates of indirect protection against influenza as it was recently demonstrated in observational studies conducted in elderly adults,” the researchers wrote.

Dr. Piedra is an ad hoc consultant for MedImmune, Novartis and Roche. – by Jennifer Southall

For more information:

Piedra P, Gaglani M, Kozinetz C, et al. Trivalent live attenuated intranasal influenza vaccine administered during the 2003-2004 influenza type A outbreak provided immediate, direct and indirect protection in children. Pediatrics. doi:10.1542/peds.2006-2836. Accessed: Aug. 13, 2007.