Efficacy of a Russian-backbone live attenuated influenza vaccine among young children in Bangladesh: a randomised, double-blind, placebo-controlled trial

Abstract

SummaryBackgroundThe rates of influenza illness and associated complications are high among children in Bangladesh. We assessed the clinical efficacy and safety of a Russian-backbone live attenuated influenza vaccine (LAIV) at two field sites in Bangladesh.MethodsBetween Feb 27 and April 9, 2013, children aged 2–4 years in urban Kamalapur and rural Matlab, Bangladesh, were randomly assigned in a 2:1 ratio, according to a computer-generated schedule, to receive one intranasal dose of LAIV or placebo. After vaccination, we monitored children in weekly home visits until Dec 31, 2013, with study clinic surveillance for influenza illness. The primary outcome was symptomatic, laboratory-confirmed influenza illness due to vaccine-matched strains. Analysis was per protocol. The trial is registered with ClinicalTrials.gov, number NCT01797029.FindingsOf 1761 children enrolled, 1174 received LAIV and 587 received placebo. Laboratory-confirmed influenza illness due to vaccine-matched strains was seen in 93 (15·8%) children in the placebo group and 79 (6·7%) in the LAIV group. Vaccine efficacy of LAIV for vaccine-matched strains was 57·5% (95% CI 43·6–68·0). The vaccine was well tolerated, and adverse events were balanced between the groups. The most frequent adverse events were tachypnoea (n=86 in the LAIV group and n=54 in the placebo group), cough (n=73 and n=43), and runny nose (n=68 and n=39), most of which were mild.InterpretationThis single-dose Russian-backbone LAIV was safe and efficacious at preventing symptomatic laboratory-confirmed influenza illness due to vaccine-matched strains. LAIV programmes might reduce the burden of influenza illness in Bangladesh.FundingThe Bill & Melinda Gates Foundation.

Efficacy of a Russian-backbone live attenuated influenza vaccine among children in Senegal: a randomised, double-blind, placebo-controlled trial

“…The absence of efficacy against strain-matched, laboratory-confirmed symptomatic influenza illness in this study contrasts with the findings of a similar study conducted in the same season with a single dose of Nasovac-S among children aged 2–4 years in Bangladesh 13 . In Bangladesh, H1N1pdm09 and H3N2 were the predominant strains, with attack rates of 3·6% and 12·3% in the placebo group, respectively, and vaccine efficacy of 50·0% (95% CI 9·2–72·5) against H1N1pdm09 and 60·4% (44·8–71·6) against H3N2.…”

“…Local symptoms, including nasal congestion, runny nose, and cough, were common among both vaccine and placebo recipients, with no imbalances between groups. These safety results are similar to those reported in Bangladesh during both a phase 2 study and the aforementioned efficacy trial there 13, 35. In view of the association of wheezing and admissions to hospital noted among children younger than 2 years who were vaccinated with FluMist, 36 we carefully monitored participants for wheezing illness using a standardised definition.…”

“…Confusing the issue further is that findings in other studies, other countries, and in other years have shown variable levels of effectiveness of live attenuated influenza vaccine against H1N1pdm09 33 . Serum Institute of India's live attenuated influenza vaccine used in Senegal and the parallel Bangladesh trial 13 also contained the E47 residue, so it is unclear how this contributed to the finding of no efficacy against H1N1pdm09 in Senegal given that efficacy was demonstrated with this vaccine in the Bangladesh trial. Finally, although standard antigenic techniques indicated circulating H1N1pdm09 was matched to vaccine, we did not sequence isolates; however, a study in Canada showed that effectiveness was preserved for current sequence changes hypothesised to result in reduced match to vaccine 34 …”

Functional immune response to influenza H1N1 in children and adults after live attenuated influenza virus vaccination

“…However, moderate protection was observed to the H1N1 strain in Europe, with 41.5% vaccine effectiveness in the UK and 47.9% in Finland, although remaining lower than IIV . A study in Senegal found that LAIV failed to protect against H1N1pdm09 in young children, whereas protection was found in a similar study in Bangladesh . The reason for these differences is currently unknown but could be due to the vaccines were being based on different backbones, or the population's exposure history .…”

Urgent challenges in implementing live attenuated influenza vaccine

“…33 LAIV has been highlighted as a particularly valuable technology given that the straightforward, high-yield manufacturing process and needle-free administration are more transferable to low-and middle-income countries and advantageous for pandemic surge production. 34 There are very few studies of LAIV in such populations but two recent RCTs assessed efficacy of "Leningrad" LAIV in Senegal 35 and Bangladesh 36 . Surprisingly, the results from these two studies are very different, with no efficacy demonstrated in Senegal, but 41% efficacy in Bangladesh ( Table 2).…”