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Review
. 2013 Dec 5;178(1):78-98.
doi: 10.1016/j.virusres.2013.05.006. Epub 2013 May 28.

H5N1 vaccines in humans

Mariana Baz  1 , Catherine J Luke, Xing Cheng, Hong Jin, Kanta Subbarao
Affiliations
Review

H5N1 vaccines in humans

Mariana Baz et al. Virus Res. .

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.

Keywords: Adjuvants; Clinical trials; H5N1; Pandemic; Vaccine strategies.

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Figures

Figure 1
Figure 1
Multi-cycle replication of recombinant wt and seasonal influenza/pandemic vaccine virus reassortants in MDCK cells. MDCK cell monolayers were inoculated with each virus at an m.o.i. of 0.001. Aliquots of supernatant were removed from duplicate wells at the timepoints shown, and virus titers were determined in MDCK cells.
Figure 2
Figure 2
Level of replication of recombinant wt and seasonal influenza/pLAIV virus reassortants in the upper respiratory tract (panels A and C) and lower respiratory tract (panels B and D) of mice, on days 2, 3 and 4 post-infection with 105 TCID50 of each virus.
Figure 2
Figure 2
Level of replication of recombinant wt and seasonal influenza/pLAIV virus reassortants in the upper respiratory tract (panels A and C) and lower respiratory tract (panels B and D) of mice, on days 2, 3 and 4 post-infection with 105 TCID50 of each virus.
Figure 3
Figure 3
Level of replication of recombinant wt and seasonal influenza/pLAIV virus reassortants in the upper and lower respiratory tract of ferrets on day 3 post-infection with 106 TCID50 of each virus.
Figure 4
Figure 4
H&E staining and IHC of lung sections from mice inoculated with the indicated viruses bearing the H5 HA.
Figure 4
Figure 4
H&E staining and IHC of lung sections from mice inoculated with the indicated viruses bearing the H5 HA.
See this image and copyright information in PMC

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