Protective efficacy of a trivalent recombinant hemagglutinin protein vaccine (FluBlok®) against influenza in healthy adults: A randomized, placebo-controlled trial

Treanor, John J.; Sahly, Hana M. El; King, James C.; Graham, Irene; Izikson, Ruvim; Kohberger, Robert; Patriarca, P.; Cox, Manon

doi:10.1016/j.vaccine.2011.07.128

Cited by 133 publications

(127 citation statements)

References 21 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…Importantly, rHA (and to a certain degree NA) vaccine candidates are currently being tested in animal models and human clinical trials with one vaccine candidate being licensed by the FDA in 2013 2,[17][18][19] . The advantage of these novel vaccines is that, due to the recombinant nature of these proteins, the labor-intensive process of generating of high growth reassortant viruses could be avoided.…”

Section: Introductionmentioning

confidence: 99%

Expression of Functional Recombinant Hemagglutinin and Neuraminidase Proteins from the Novel H7N9 Influenza Virus Using the Baculovirus Expression System

Margine

Palese

Krammer

2013

JoVE

146

View full text Add to dashboard Cite

The baculovirus expression system is a powerful tool for expression of recombinant proteins. Here we use it to produce correctly folded and glycosylated versions of the influenza A virus surface glycoproteins -the hemagglutinin (HA) and the neuraminidase (NA). As an example, we chose the HA and NA proteins expressed by the novel H7N9 virus that recently emerged in China. However the protocol can be easily adapted for HA and NA proteins expressed by any other influenza A and B virus strains. Recombinant HA (rHA) and NA (rNA) proteins are important reagents for immunological assays such as ELISPOT and ELISA, and are also in wide use for vaccine standardization, antibody discovery, isolation and characterization. Furthermore, recombinant NA molecules can be used to screen for small molecule inhibitors and are useful for characterization of the enzymatic function of the NA, as well as its sensitivity to antivirals. Recombinant HA proteins are also being tested as experimental vaccines in animal models, and a vaccine based on recombinant HA was recently licensed by the FDA for use in humans. The method we describe here to produce these molecules is straight forward and can facilitate research in influenza laboratories, since it allows for production of large amounts of proteins fast and at a low cost. Although here we focus on influenza virus surface glycoproteins, this method can also be used to produce other viral and cellular surface proteins. Video LinkThe video component of this article can be found at

show abstract

Section: Introductionmentioning

confidence: 99%

Expression of Functional Recombinant Hemagglutinin and Neuraminidase Proteins from the Novel H7N9 Influenza Virus Using the Baculovirus Expression System

Margine

Palese

Krammer

2013

JoVE

146

View full text Add to dashboard Cite

show abstract

“…The most advanced egg-free flu vaccine candidate is a recombinant multimeric H5 hemagglutinin protein (rH5) produced by using a baculovirus expression vector system in SF+ insect cells (1,2). Previous clinical studies suggested that two 90-μg doses of rH5 induced modest responses equivalent to conventional subvirion-based H5N1 vaccines (3,4).…”

mentioning

confidence: 99%

Adjuvant solution for pandemic influenza vaccine production

Clegg

Roque

Hoeven

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Extensive preparation is underway to mitigate the next pandemic influenza outbreak. New vaccine technologies intended to supplant egg-based production methods are being developed, with recombinant hemagglutinin (rHA) as the most advanced program for preventing seasonal and avian H5N1 Influenza. Increased efforts are being focused on adjuvants that can broaden vaccine immunogenicity against emerging viruses and maximize vaccine supply on a worldwide scale. Here, we test protection against avian flu by using H5N1-derived rHA and GLA-SE, a two-part adjuvant system containing glucopyranosyl lipid adjuvant (GLA), a formulated synthetic Toll-like receptor 4 agonist, and a stable emulsion (SE) of oil in water, which is similar to the best-in-class adjuvants being developed for pandemic flu. Notably, a single submicrogram dose of rH5 adjuvanted with GLA-SE protects mice and ferrets against a high titer challenge with H5N1 virus. GLA-SE, relative to emulsion alone, accelerated induction of the primary immune response and broadened its durability against heterosubtypic H5N1 virus challenge. Mechanistically, GLA-SE augments protection via induction of a Th1-mediated antibody response. Innate signaling pathways that amplify priming of Th1 CD4 T cells will likely improve vaccine performance against future outbreaks of lethal pandemic flu.

show abstract

“…Protein Sciences has created the trivalent HA epitope vaccine (Flublok), which is the only licensed and approved flu vaccine that does not use eggs, antibiotics, or live influenza virus in any part of the manufacturing process. Their system uses an insect virus (baculovirus) expression system to produce influenza antigenic proteins (82). Medicago is in phase II clinical trials with an influenza viruslike particle vaccine expressed in and purified from tobacco (37) and using a process that can reduce vaccine production times by 33%.…”

Section: New Research Opportunitiesmentioning

confidence: 99%

Adapting global influenza management strategies to address emerging viruses

Noah

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Death by respiratory complications from influenza infections continues to be a major global health concern. Antiviral drugs are widely available for therapy and prophylaxis, but viral mutations have resulted in resistance that threatens to reduce the long-term utility of approved antivirals. Vaccination is the best method for controlling influenza, but vaccine strategies are blunted by virus antigenic drift and shift. Genetic shift in particular has led to four pandemics in the last century, which have prompted the development of efficient global surveillance and vaccination programs. Although the influenza pandemic of 2009 emphasized the need for the rapid standardization of global surveillance methods and the preparation and dissemination of global assay standards for improved reporting and diagnostic tools, outbreaks of novel influenza strains continue to occur, and current efforts must be enhanced by aggressive public education programs to promote increased vaccination rates in the global population. Recently, a novel H7N9 avian influenza virus with potential to become a pandemic strain emerged in China and was transmitted from animals to humans with a demonstrated >20% mortality rate. Sporadic outbreaks of highly lethal avian virus strains have already increased public awareness and altered annual vaccine production strategies to prevent the natural adaption of this virus to human-to-human transmission. Additional strategies for combating influenza include advancement of new antivirals for unexploited viral or host cellular targets; novel adjuvants and alternate vaccine delivery systems; and development of universal protein, DNA, or multivalent vaccines designed to increase immune responsiveness and enhance public health response times.

show abstract

Protective efficacy of a trivalent recombinant hemagglutinin protein vaccine (FluBlok®) against influenza in healthy adults: A randomized, placebo-controlled trial

Cited by 133 publications

References 21 publications

Expression of Functional Recombinant Hemagglutinin and Neuraminidase Proteins from the Novel H7N9 Influenza Virus Using the Baculovirus Expression System

Expression of Functional Recombinant Hemagglutinin and Neuraminidase Proteins from the Novel H7N9 Influenza Virus Using the Baculovirus Expression System

Adjuvant solution for pandemic influenza vaccine production

Adapting global influenza management strategies to address emerging viruses

Contact Info

Product

Resources

About