LAIV vs. TIV in children
The relative protection by the two types of vaccination in children were first evaluated in Belshe et al, and Halloran et al. Belshe compared TIV and LAIV in an international, randomised, double-blinded study involving 8352 children from the ages of 6-59 months (Fig. X). Children were first split into two groups those who had received a prior influenza vaccination, and those that had not. Those that had received prior influenza vaccination were given one dose, and those in the other group were given two doses of vaccine. This was important in ensuring both vaccine groups would be well matched in terms of demographic characteristics, not only did they take into consideration prior vaccination (22%), but also history of wheezing (21%), recurrent wheezing (6%), and asthma (4%). The endpoint in the investigation was the “incidence of culture‐confirmed modified Centers for Disease Control and Prevention (CDC) influenza‐like illness (ILI)” which was defined as fever plus ≥1 other symptom of cough, sore throat, or nasal congestion.
There were 45% (95% CI: 22, 61) fewer cases of influenza caused by matched strains in LAIV recipients than TIV recipients (53/3916 versus 93/3936, respectively), and 58% (95% CI: 47, 67) fewer cases caused by mismatched strains (102/3916 versus 245/3936, respectively). Efficacy was consistent across age groups.
The incidence rates caused by matched strains in LAIV patients were 45% (95% CI: 22, 61) lower compared to TIV patients (53/3916 vs. 93/3936, respectively. The incidence rate was also 58% (95% CI: 47, 67) fewer in LAIV patients compared to TIV patients when caused by mismatched strains. In terms of B lineage strains LAIV showed a relative efficacy of 27%, compared to the TIV vaccine however this difference was not significant and therefore cannot be considered in the conclusion.
The incidence of serious adverse effects did not differ significantly between the two groups, however post hoc the rates of hospitalization amongst infants aged 6 to 11 months were significantly higher in the live-attenuated-vaccine group compared with that of the inactivated-vaccine group. These observations need to be studied further to obtain a definitive answer.
Halloran on the other hand conducted a large, open‐label, non‐randomized trial in the U.S.A. during the 2003-04-influenza season. The study showed that LAIV was effective against the mismatched A/Fujian/411/02 (H3N2) virus by preventing the number of acute respiratory illness amongst children aged between 5–18 years, it also highlighted that there was no effectiveness seen when TIV was administered. When comparing the vaccine effectiveness children were grouped into the age ranges of 5-9 and 10-18 years old however the efficacy was similar between both groups. Nevertheless it is difficult to compare both the LAIV and TIV groups effectively due to their differing baseline characteristics.
LAIV vs. TIV in adults
Treanor et al first compared the relative protection between both types of vaccine in a placebo‐controlled, double‐blind study. The interventions were given to subjects who had a baseline serum hemagglutination‐inhibition (HAI) antibody titre ≤1:8, they were then challenged intranasally with a vaccine-like wild virus 28 days after the intervention was administered. In terms of the findings from the paper, 45% (14/31) of subjects who received the placebo were found to have had laboratory documented influenza illness, compared with 6.9% (2/29) and 12.5% (4/32) from the LAIV and TIV groups respectively.
As seen in figure X the protective efficacy was 85% (95% CI: 28, 100) for LAIV and 71% (95% CI: 2, 97) for TIV. LAIV had a lower mean symptom score than both the TIV and placebo, additionally there were trends towards less severe illness in the LAIV group.
The next series of papers selected that compared both the LAIV and TIV vaccines were those written by Ohmit et al, where University of Michigan compared the efficacy of a single dose of LAIV and TIV on the state campus for the influenza seasons 2005-2006 and 2007-2008. The main drawback with this study was that the number of participants of age >25 were 30% and 22% respectively. The studies were randomised with double blinding for vaccine vs. placebo however they were open-label for nasal spray vs. injection. The observed efficacy for TIV and LAIV were 74-77% and 48-57% respectively, the difference between the two types of vaccination route were not statistically significant. Additionally in the placebo group during the 2005-2006 season the influenza rate observed was much lower than in the 2004-2005 season (1.8% vs. 7.8%) rendering the trial underpowered to identify vaccine efficacy. When using viral culture the relative efficacy of TIV vs. LAIV was 45% (95% CI: 3, 69) compared to a relative efficacy of 50% (95% CI: 20, 69) when using PCR. Furthermore within these papers they compared the local and systemic reactions to TIV and LAIV vaccines within 7 days as noted in figure X. LAIV has been associated with increased rates of runny noses; sore throat, cough, and headache in adults. Comparatively TIV has been linked with increased rates of injection site reaction and fever, muscle aches, and oculo-respiratory syndromes in adults. No analysis of illness severity among breakthrough cases was reported for any of the study seasons.
Since 2004 the United States of America have had the objective to vaccinate all personnel annually with either LAIV or TIV to ensure more efficiently when working in the field. Wang et al conducted a retrospective cohort study for service members aged between 17–49 years who had received LAIV or TIV during the 2004–2005, 2005–2006, or 2006–2007 seasons. To control any covariates such as age, sex, medical and immunisation history a multivariant Poisson regression model was used with pensity-based matching. The primary end point was when a subject was given a diagnosis associated with pneumonia or influenza this was due to the fact that no laboratory confirmation of influenza was available. This evidently isn’t the best end point, as not all subjects would present to a healthcare professional with signs of an influenza-like disease. The group who received no form of immunisation had the highest incidence rate; additionally it was lower in the TIV group compared to the LAIV group. Adjusted incidence rate ratios were used to compare LAIV vs. TIV vaccinated this ranged from 1.25-1.75.
Originally published 15.10.2019