Assessing the Evidence Live Attenuated Influenza Vaccine in Children Younger than 2 Years. A Systematic Review
ABSTRACT Live attenuated influenza vaccine (LAIV) is effective in children but contraindicated in children <2 years of age.
We searched Medline, EMBASE, the Cochrane Library, Web of Science, Scopus, PsycInfo and CINAHL through February 2013 for existing systematic reviews, randomized controlled trials (RCTs) and observational studies (for safety). We included studies enrolling healthy children <2 years of age who received LAIV, compared with placebo or inactivated influenza vaccine (IIV). Data were extracted independently by 2 investigators. The relative risk (RR) was pooled across studies using the random effects model.
We found 7 eligible randomized controlled trials and 2 observational studies. Randomized controlled trials included 6281 children and were at low to moderate risk of bias. LAIV reduced the incidence of influenza compared with placebo (relative risk = 0.36, 95% confidence interval: 0.23-0.58, P < 0.05) with a number needed to vaccinate of 17. LAIV increased the incidence of minor side effects (fever and rhinorrhea). LAIV had a similar effect in preventing influenza (relative risk = 0.76, 95% confidence interval: 0.45-1.30, P > 0.05) compared with inactivated influenza vaccine. There was an increase of hospitalization rate (post hoc analysis) and medical attended wheezing with LAIV.
LAIV is highly effective in children <2 years of age compared with placebo and is as effective to inactivated influenza vaccine. The safety profile of LAIV is reasonable although evidence is sparse. LAIV may be considered as an option in this age group particularly during seasons with vaccine shortage.
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ABSTRACT: The small hydrophobic (SH) gene of respiratory syncytial virus (RSV), a major cause of infant hospitalisation, encodes a viroporin of unknown function. SH gene knockout virus (RSV ΔSH) is partially attenuated in vivo but not in vitro, suggesting that the SH protein may have an immunomodulatory role. RSV ΔSH has been tested as a live attenuated vaccine in humans and cattle and here we demonstrate that it protected against viral re-challenge in mice. We compared the immune response to infection with wild type and ΔSH RSV, in vivo using BALB/c mice and in vitro using epithelial cells, neutrophils and macrophages. Strikingly, the IL-1β response to RSV ΔSH infection was greater than wild type RSV, in spite of decreased viral load and when IL-1β was blocked in vivo, viral load returned to wild type levels. A significantly higher IL-1β response to RSV ΔSH was also detected in vitro, with greater magnitude responses in neutrophils and macrophages than epithelial cells. Depleting macrophages (with clodronate liposome) and neutrophils (with anti-Ly6G/1A8) demonstrated the contribution of these cells to the IL-1β response in vivo, the first demonstration of neutrophilic IL-1β production in response to viral lung infection. In this study we describe an increased IL-1β response to RSV ΔSH, which may explain the attenuation in vivo and supports targeting the SH gene in live attenuated vaccines. There is a pressing need for a vaccine for Respiratory Syncytial Virus (RSV). A number of live attenuated RSV vaccine strains have been developed in which the small hydrophobic (SH) gene has been deleted, even though the function of the SH protein is unknown. The structure of the SH protein has recently been solved showing it is a pore forming protein (viroporin). Here we demonstrate that the IL-1β response to RSV ΔSH is greater in spite of lower viral load, which contributes to the attenuation in vivo. This potentially suggests a novel method by which viruses can evade the host response. As all Pneumovirinae and some Paramyxovirinae encode similar SH genes this new understanding may also enable the development of live attenuated vaccines for both RSV and other members of the Paramyxoviridae. Copyright © 2015, American Society for Microbiology. All Rights Reserved.Journal of Virology 06/2015; 89(17). DOI:10.1128/JVI.01070-15 · 4.44 Impact Factor
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ABSTRACT: One of the earliest methods used in the manufacture of stable and safe vaccines is the use of chemical and physical treatments to produce inactivated forms of pathogens. Although these types of vaccines have been successful in eliciting specific humoral immune responses to pathogen-associated immunogens, there is a large demand for the development of fast, safe, and effective vaccine manufacturing strategies. Radiation sterilization has been used to develop a variety of vaccine types, because it can eradicate chemical contaminants and penetrate pathogens to destroy nucleic acids without damaging the pathogen surface antigens. Nevertheless, irradiated vaccines have not widely been used at an industrial level because of difficulties obtaining the necessary equipment. Recent successful clinical trials of irradiated vaccines against pathogens and tumors have led to a reevaluation of radiation technology as an alternative method to produce vaccines. In the present article, we review the challenges associated with creating irradiated vaccines and discuss potential strategies for developing vaccines using radiation technology.07/2015; 4(2):145-58. DOI:10.7774/cevr.2015.4.2.145