Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin

Song, Langzhou; Zhang, Yi; Yun, Nadezhda E.; Poussard, Allison; Smith, Jeanon N.; Smith, Jennifer K.; Borisevich, Viktoriya; Linde, Jenna; Zacks, Michele A.; Li, Hong; Kavita, Uma; Reiserová, Lucia; Liu, Xiangyu; Dumuren, Kunmi; Balasubramanian, Bhuvaneswari; Weaver, Bruce; Parent, Jason; Umlauf, Scott; Liu, Ge; Huleatt, Jim; Tussey, Lynda; Paessler, Slobodan

doi:10.1016/j.vaccine.2009.07.060

Cited by 79 publications

(76 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1A to C), eliciting robust neutralizing antibody responses by linking innate immunity and adaptive immunity. Candidate influenza vaccines based on this platform, in which the globular head of influenza hemagglutinin (HA) was fused to Salmonella enterica serovar Typhimurium FljB flagellin phase 2 (STF2) at the carboxyl terminus, replacing domain 3 (R3), or at both the C-terminal and R3 positions (R3.2x), were demonstrated to be immunogenic and efficacious in mice (19)(20)(21) and ferrets (22). More importantly, these vaccine candidates are well tolerated and immunogenic in humans (23,24).…”

Section: E Domain I (Ei) Is the Central Domain And E Domain Ii (Eii)mentioning

confidence: 99%

Immunogenicity and Efficacy of Flagellin-Envelope Fusion Dengue Vaccines in Mice and Monkeys

Liu

Song

Putnak

et al. 2015

Clin. Vaccine Immunol.

Self Cite

View full text Add to dashboard Cite

The envelope (E) protein of flaviviruses includes three domains, EI, EII, and EIII, and is the major protective antigen. Because EIII is rich in type-specific and subcomplex-specific neutralizing epitopes and is easy to express, it is particularly attractive as a recombinant vaccine antigen. VaxInnate has developed a vaccine platform that genetically links vaccine antigens to bacterial flagellin, a Toll-like receptor 5 ligand. Here we report that tetravalent dengue vaccines (TDVs) consisting of four constructs, each containing two copies of EIII fused to flagellin (R3.2x format), elicited robust and long-lived neutralizing antibodies (geometric mean titers of 200 to 3,000), as measured with a 50% focus reduction neutralization test (FRNT 50 ). In an immunogenicity study, rhesus macaques (n ‫؍‬ 2) immunized subcutaneously with 10 g or 90 g of TDV three or four times, at 4-to 6-week intervals, developed neutralizing antibodies to four dengue virus (DENV) serotypes (mean post-dose 3 FRNT 50 titers of 102 to 601). In an efficacy study, rhesus macaques (n ‫؍‬ 4) were immunized intramuscularly with 16 g or 48 g of TDV or a placebo control three times, at 1-month intervals. The animals that received 48-g doses of TDV developed neutralizing antibodies against the four serotypes (geometric mean titers of 49 to 258) and exhibited reduced viremia after DENV-2 challenge, with a group mean viremia duration of 1.25 days and 2 of 4 animals being completely protected, compared to the placebo-treated animals, which all developed viremia, with a mean duration of 4 days. In conclusion, flagellin-EIII fusion vaccines are immunogenic and partially protective in a nonhuman primate model. Dengue disease poses a significant health threat to almost onehalf of the world's population residing in the Asian-Pacific region and Latin America, where the disease is endemic, as well as to travelers and military personnel. Currently, no licensed dengue vaccine is available. Several vaccine candidates based on live attenuated dengue viruses (DENVs) or dengue virus-flavivirus chimeras are currently being evaluated in phase II or III clinical trials (for reviews, see references 1-3). However, some of these vaccines require lengthy immunization regimens of up to 1 year for the development of immunity to all four serotypes, which seems to make them less well suited for travelers and military personnel. In a series of recently published phase IIb/III trials conducted in five Asian countries in which dengue is endemic, the Sanofi-Aventis chimeric yellow fever (YF) 17D-DENV-1 to -4 CYD tetravalent dengue vaccine (TDV) showed an acceptable safety profile and 56% overall efficacy (4); however, the vaccine failed to confer significant protection against DENV-2 (5). These findings underscore the need for the development of alternative vaccine platforms, such as those based on purified inactivated virus (6), DNA (7), and recombinant subunit truncated envelope (E) proteins (e.g., 80% envelope protein [80E]) (8). Some of these alternative vaccine candidates hav...

show abstract

Section: E Domain I (Ei) Is the Central Domain And E Domain Ii (Eii)mentioning

confidence: 99%

Immunogenicity and Efficacy of Flagellin-Envelope Fusion Dengue Vaccines in Mice and Monkeys

Liu

Song

Putnak

et al. 2015

Clin. Vaccine Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The fusion strategy can be achieved by inserting vaccine target antigen at the N-terminus or C-terminus or within the hypervariable region of the flagellin. A number of vaccine candidates with this strategy have reached early stage clinical studies, and this represents one of the most promising new directions in vaccine development [13,14,[17][18][19].…”

Section: Enhancement Of Salivary Siga Antibodies and Anti-caries Protmentioning

confidence: 99%

“…Flagellin as the ligand of toll-like receptor 5 (TLR5) has been proven to be an effective mucosal adjuvant and become promising for clinical use [13][14][15][16][17][18][19]. We applied the recombinant flagellin as mucosal adjuvant in anti-caries vaccines by nasal immunization, either using flagellin directly by simple mixing with antigen or using fusion strategy to combine flagellin and the target antigen in a single fusion protein, proved the efficacy for enhancement of specific IgA response in oral fluids and better protection against caries [11,20,21].…”

mentioning

confidence: 99%

Salivary IgA enhancement strategy for development of a nasal-spray anti-caries mucosal vaccine

Yan

2013

Sci. China Life Sci.

View full text Add to dashboard Cite

Dental caries remains one of the most common global chronic diseases caused by Streptococcus mutans, which is prevalent all over the world. The caries prevalence of children aged between 5-6 years old in China is still in very high rate. A potent and effective anti-caries vaccine has long been expected for caries prevention but no vaccines have been brought to market till now mainly due to the low ability to induce and maintain protective antibody in oral fluids. This review will give a brief historical retrospect on study of dental caries and pathogenesis, effective targets for anti-caries vaccines, oral immune system and immunization against dental caries. Then, salivary IgA antibodies and the protective responses are discussed in the context of the ontogeny of mucosal immunity to indigenous oral streptococcal. The methods and advancement for induction of specific anticaries salivary sIgA antibodies and enhancement of specific anti-caries salivary sIgA antibodies by intranasal immunization with a safe effective mucosal adjuvant are described. The progress in the enhancement of salivary sIgA antibodies and anticaries protection by intranasal immunization with flagellin-PAc fusion protein will be highlighted. Finally, some of the main strategies that have been used for successful mucosal vaccination of caries vaccine are reviewed, followed by discussion of the mucosal adjuvant choice for achieving protective immunity at oral mucosal membranes for development of a nasal-spray or nasal-drop anti-caries vaccine for human. mutans streptococci, secretory IgA, PAc, mucosal immunization, caries vaccine Citation:Yan H M. Salivary IgA enhancement strategy for development of a nasal-spray anti-caries mucosal vaccine.

show abstract

“…The intensive response to flagellin is mediated by toll-like receptor 5, linking innate and adaptive immunity11. Because of this, a powerful vaccine can be created by fusion of flagellin with an antigen [411].…”

Section: Flagellinmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

View full text Add to dashboard Cite

show abstract

Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin

Cited by 79 publications

References 40 publications

Immunogenicity and Efficacy of Flagellin-Envelope Fusion Dengue Vaccines in Mice and Monkeys

Immunogenicity and Efficacy of Flagellin-Envelope Fusion Dengue Vaccines in Mice and Monkeys

Salivary IgA enhancement strategy for development of a nasal-spray anti-caries mucosal vaccine

Selection of Adjuvants for Enhanced Vaccine Potency

Contact Info

Product

Resources

About