Study: Good antibody response to one or two doses of LAIV

Hoft DF. J Infect Dis. 2011;doi:10.1093/infdis/jir436.

Children aged younger than 3 years receive the same protective antibody response from the recommended two doses of seasonal influenza vaccines, regardless of whether the doses were from the live-attenuated influenza vaccine or the trivalent inactivated vaccine, according to research published online.

Daniel F. Hoft, MD, PhD, of the division of infectious diseases, allergy and immunology, Saint Louis University School of Medicine, Vaccine Treatment and Evaluation Unit, and colleagues looked at data from 53 children aged 6 to 35 months during the 2005-2006 and 2006-2007 influenza seasons.

During the study, all children received an initial dose of licensed seasonal influenza vaccine and a booster dose 1 month later. In two groups, the vaccines matched, with children receiving two injections of a TIV injection or two nasal spray LAIVs (FluMist, MedImmune). Children in the other two groups received a combination of vaccines, with a dose of LAIV given either before or after TIV.

The researchers found that all four dosing patterns were safe and induced similar levels of protective antibodies. However, when the investigators looked at responses from the T-cell arm of the immune system, they could not detect influenza-specific T cells in children who received only TIV.

“Only LAIV induced CD4, CD8, and T cells relevant for broadly protective heterosubtypic immunity,” the researchers said.

Children who received only one dose of LAIV had T-cell responses similar to those who received two, and the order of vaccine types did not make a significant difference in the size of the T-cell response. However, because LAIV has sometimes been associated with increased incidence of wheezing in the youngest recipients, the results of this trial suggest that the best regimen for children aged younger than 24 months may be TIV followed by LAIV, Hoft said. Larger clinical trials are required to confirm the safety and efficacy of such an approach, he added.

Infectious Diseases in Children Editorial Board members Kathryn M. Edwards, MD, and C. Buddy Creech, MD, MPH, were co-investigators of the study.

Eugene Shapiro

It is recommended that young children (beginning as early as 6 months of age) receive two doses of influenza vaccine the first time they are immunized against influenza. Although studies indicate that trivalent live-attenuated (cold-adapted) influenza vaccine (LAIV) is more effective in preventing influenza in children than is trivalent inactived influenza vaccine (TIV), LAIV cannot be given to children aged younger than 24 months because of the risk of inducing an attack of asthma. The investigators undertook a small pilot study to assess the safety and effects of two doses of each possible sequence of these two vaccines administered a month apart. Conceivably, if a dose LAIV administered after an initial dose of TIV was safe and not associated with increased risk of adverse effects, young children might be able to receive the additional benefit of LAIV. Of course, definitive demonstration of this would require a large clinical trial.

Joseph A. Bocchini

The investigators assessed safety as well as immunogenicity and induction of influenza-specific T-cell memory by different combinations of these two vaccines in a small number (n=56) of healthy children aged 6-35 months. They found all combinations of these vaccines to be safe and immunogenic for development of humoral immunity (specific hemagglutination inhibition antibodies against the influenza viruses contained in the vaccine). However, only children who received LAIV developed T-cell memory against highly conserved epitopes of influenza virus that could conceivably provide heterotypic immunity against types of influenza virus not contained in the trivalent vaccines. This occurred regardless of whether the child received LAIV as the first, second or both does. In addition, the investigators found that T-cells from children who had received LAIV were much more likely than were T-cells from children who had received only TIV to inhibit replication of influenza virus in cell culture (including heterotypic viruses not specifically included in the vaccine). Moreover, children who received LAIV for their first dose (vaccine virus was recovered from 61% of these children) were significantly less likely to shed the vaccine virus after a second dose of LAIV (8%).

However, although shedding of the vaccine virus was lower (30%) in children who received LAIV as a second dose if they had been previously primed with TIV compared with children who received LAIV as a first dose (61%), this difference was not statistically significant. However, because of the small number of children in each group, the statistical power to demonstrate a significant difference was poor.

This study is important because it demonstrates a possible explanation for the greater protection afforded by LAIV. It induces cell-mediated immunity with T-cell memory, immunity that could also provide some protection against strains of influenza not included in the vaccine. All of the combinations of the vaccines were safe in this small pilot study, but a much larger study is needed to confirm the safety of this approach. While the in vitro data demonstrate possible reasons to encourage wider use of LAIV, even if the numbers were large enough that decrease in viral shedding after administration of LAIV among children who had received their initial dose of vaccine as TIV was statistically significant, a substantial number (nearly one-third) of these children still shed the virus. Larger studies are needed to confirm the safety and effectiveness of this approach, but this is an encouraging start.

Joseph A. Bocchini, MD
Eugene Shapiro, MD
Infectious Diseases in Children Editorial Board members

Disclosures: Drs. Bocchini and Shapiro report no relevant financial disclosures.

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