Safety and Immunogenicity of a Prepandemic Influenza A (H5N1) Vaccine in Children
ABSTRACT The avian influenza A (H5N1) virus is considered to be a potential cause of the next influenza pandemic. Children may be particularly vulnerable to the pandemic virus, and they may react differently than adults to vaccines. We report the results of the first clinical trial of an H5N1 vaccine in children.
Twelve healthy children (mean age +/- SD: 12.73 +/- 2.77 years) received a single dose of 6 microg of the inactivated whole virus vaccine Fluval. Twenty-one days after vaccination, immunogenicity was assessed by hemagglutination inhibition and microneutralization assays. Safety information was collected for 180 days.
No side-effects were observed, and the vaccine fulfilled all applicable U.S. and European immunogenicity criteria for licensure. The post/prevaccination geometric mean titer ratio was 16.95, the rate of seroconversion was 75% and the rate of seroprotection was also 75% 21 days after vaccination.
We confirmed our earlier findings of the present vaccine in adults showing encouraging safety and immunogenicity properties in children. Studies with the present vaccine in elderly subjects are underway.
SourceAvailable from: Haixia Xiao[Show abstract] [Hide abstract]
ABSTRACT: To combat the possibility of a zoonotic H5N1 pandemic in a timely fashion, it is necessary to develop a vaccine that would confer protection against homologous and heterologous human H5N1 influenza viruses. Using a replicating modified vaccinia virus Tian Tan strain (MVTT) as a vaccine vector, we constructed MVTTHA-QH and MVTTHA-AH, which expresses the H5 gene of a goose-derived Qinghai strain A/Bar-headed Goose/Qinghai/1/2005 or human-derived Anhui Strain A/Anhui/1/2005. The immunogenicity profiles of both vaccine candidates were evaluated. Vaccination with MVTTHA-QH induced a significant level of neutralizing antibodies (Nabs) against a homologous strain and a wide range of H5N1 pseudoviruses (clades 1, 2.1, 2.2, 2.3.2, and 2.3.4). Neutralization tests (NT) and Haemagglutination inhibition (HI) antibodies inhibit the live autologous virus as well as a homologous A/Xingjiang/1/2006 and a heterologous A/Vietnam/1194/2004, representing two human isolates from clade 2.2 and clade 1, respectively. Importantly, mice vaccinated with intranasal MVTTHA-QH were completely protected from challenge with lethal dosages of A/Bar-headed Goose/Qinghai/1/2005 and the A/Viet Nam/1194/2004, respectively, but not control mice that received a mock MVTTS vaccine. However, MVTTHA-AH induced much lower levels of NT against its autologous strain. Our results suggest that it is feasible to use the H5 gene from A/Bar-headed Goose/Qinghai/1/2005 to construct an effective vaccine, when using MVTT as a vector, to prevent infections against homologous and genetically divergent human H5N1 influenza viruses.PLoS ONE 12/2013; 8(12):e83274. DOI:10.1371/journal.pone.0083274 · 3.53 Impact Factor
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ABSTRACT: No examination of simultaneous vaccination against pandemic H1N1 and the seasonal influenza virus strains, in children with cancer receiving chemotherapy, are yet published. We investigated the immunogenicity of a whole-virion, inactivated, adjuvanted pandemic H1N1, and seasonal influenza vaccines administered simultaneously to children with cancer undergoing chemotherapy. We prospectively enrolled 27 pediatric patients receiving therapy for various types of cancer. All received influenza vaccination once in a seasonal risk period. We checked hemaglutination-inhibition (HAI) antibody titers in the sera of patients before, and 21-28 days after vaccination. Seroprotective titer was defined as an antibody titer ≥40, and seroresponse as ≥4-fold increase in antibody titers after vaccination. The pre- and post-vaccination seroprotective rates were H1N1: 33-48%, H3N2: 56-78%, B: 0-15% for seasonal influenza, and for pandemic H1N1: 15-37%. The seroresponse rates for seasonal influenza H1N1, H3N2, and B were 22%, 37%, and 22%, respectively, and 30% for the pandemic H1N1 vaccine. Whole-virion, inactivated, adjuvanted vaccine for the pandemic H1N1 Influenza A virus and the seasonal influenza vaccines were found safe and partially immunogenic in children with cancer receiving chemotherapy. The only determinants of responsiveness were lymphocyte count and serum immunoglobulin-G. Only influenza B vaccine elicited significant differences in differences in pre- and post-vaccination seroprotective rates. The response to vaccination for pandemic H1N1 is as effective as other vaccines, however administration of a single vaccine during chemotherapy is more comfortable for pediatric cancer patients. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.Pediatric Blood & Cancer 06/2014; 61(6). DOI:10.1002/pbc.24893 · 2.56 Impact Factor
Article: H5N1 vaccines in humans.[Show abstract] [Hide abstract]
ABSTRACT: The spread of highly pathogenic avian H5N1 influenza viruses since 1997 and their virulence for poultry and humans has raised concerns about their potential to cause an influenza pandemic. Vaccines offer the most viable means to combat a pandemic threat. However, it will be a challenge to produce, distribute and implement a new vaccine if a pandemic spreads rapidly. Therefore, efforts are being undertaken to develop pandemic vaccines that use less antigen and induce cross-protective and long-lasting responses, that can be administered as soon as a pandemic is declared or possibly even before, in order to prime the population and allow for a rapid and protective antibody response. In the last few years, several vaccine manufacturers have developed candidate pandemic and pre-pandemic vaccines, based on reverse genetics and have improved the immunogenicity by formulating these vaccines with different adjuvants. Some of the important and consistent observations from clinical studies with H5N1 vaccines are as follows: two doses of inactivated vaccine are generally necessary to elicit the level of immunity required to meet licensure criteria, less antigen can be used if an oil-in-water adjuvant is included, in general antibody titers decline rapidly but can be boosted with additional doses of vaccine and if high titers of antibody are elicited, cross-reactivity against other clades is observed. Prime-boost strategies elicit a more robust immune response. In this review, we discuss data from clinical trials with a variety of H5N1 influenza vaccines. We also describe studies conducted in animal models to explore the possibility of reassortment between pandemic live attenuated vaccine candidates and seasonal influenza viruses, since this is an important consideration for the use of live vaccines in a pandemic setting.Virus Research 05/2013; DOI:10.1016/j.virusres.2013.05.006 · 2.83 Impact Factor