Preclinical development of a dengue tetravalent recombinant subunit vaccine: Immunogenicity and protective efficacy in nonhuman primates

Govindarajan, Dhanasekaran; Meschino, Steven; Guan, Liming; Clements, David E.; Meulen, Jan H. ter; Casimiro, Danilo R.; Coller, Beth-Ann; Bett, Andrew J.

doi:10.1016/j.vaccine.2015.06.067

Cited by 65 publications

(68 citation statements)

References 33 publications

(16 reference statements)

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“…PRNT was performed on acute-phase sera to detect neutralization antibody to ZIKV as reported previously (47). For late convalescent-phase sera, a previously described micro-neutralization test was performed (48). Briefly, flat-bottom 96-well plates were seeded with Vero cells (3 × 10 4 cells per well) 24 h prior to infection.…”

Section: Methodsmentioning

confidence: 99%

T cell responses to nonstructural protein 3 distinguish infections by Dengue and Zika viruses

Herrera

Tsai

Brites

et al. 2018

Preprint

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WORD COUNT: 229 24 25 TEXT WORD COUNT: 3,409 26 27 (ZIKV) epidemic in the Americas and the Caribbean 49 demonstrates that clinical assays to detect, distinguish, and characterize immune 50 responses to flaviviral infections are needed. ZIKV and dengue virus (DENV) are 51 mosquito-transmitted flaviviruses sharing overlapping geographical distribution and 52have significant sequence similarity that can increase the potential for antibody and T 53 cell cross-reaction. Using nonstructural protein 1-based enzyme-linked immunosorbent 54 assays (ELISAs), we determine the serostatus of individuals living in a DENV-and 55 ZIKV-endemic region in Brazil, identifying individuals with primary DENV (pDENV) and 56 ZIKV (pZIKV), ZIKV with primary DENV (ZIKVwpDENV), and secondary DENV 57 (sDENV) infections; pDENV and pZIKV were further confirmed by neutralization tests. 58Development of an enzyme-linked immunospot (ELISPOT) assay for DENV and ZIKV 59 structural and nonstructural (NS) protein antigens enables us to distinguish infections by 60 these viruses based on T cells and to characterize those responses. We find that IFN-γ 61 and TNF-α T cell responses to NS3 differentiates DENV and ZIKV infections with 94% 62 sensitivity and 92% specificity. In general, we also show that pDENV and sDENV cases 63 and pZIKV and ZIKVwpDENV cases elicit similar T cell response patterns, and that HIV-64 infected individuals have T cell responses that are lower in magnitude compared to HIV-65 negative individuals. These results have important implications for DENV and ZIKV 66 diagnostic and vaccine development and provide critical insights into the T cell 67 response in individuals with multiple flaviviral infections. 68 69 4 IMPORTANCE 70 71 The potential for antibody and T cell cross-reaction to DENV and ZIKV, 72 flaviviruses that co-circulate and can sequentially infect individuals, has complicated 73 diagnostic and vaccine development. Our serological data show that antibodies to 74 nonstructural protein 1 can distinguish sequential human infections by DENV and ZIKV. 75 The development of a simple and inexpensive assay also enables the differentiation of 76 DENV and ZIKV infections based on the characterization of T cell responses. Our T cell 77 data reveals strong response patterns that are similar in nature in individuals with one or 78 multiple DENV infections and in individuals with only primary ZIKV infection and ZIKV-79 infected individuals with previous DENV exposure. The characterization of T cell 80 responses in a serologically-validated group of individuals is of relevance to the 81 development of vaccines and immunotherapeutics against these global threats. 82 83 84 85 86 87 88 89 90 91 92 93 94 Aedes mosquitoes transmit globally relevant flaviviruses including dengue virus 95 (DENV) and Zika virus (ZIKV). DENV exists as four antigenic serotypes, DENV1 to 96 DENV4 (1). These viruses have a wide geographic distribution with approximately 390 97 million infections annually and more than a quarter of the world's population at risk (2)...

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Section: Methodsmentioning

confidence: 99%

T cell responses to nonstructural protein 3 distinguish infections by Dengue and Zika viruses

Herrera

Tsai

Brites

et al. 2018

Preprint

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“…The resultant cell line, Drosophila Schneider line 2, is today used as a stable, nonviral and nonlytic expression system able to successfully produce difficult to express proteins and suitable for cultivation using batch, fed-batch, and continuous cultivation techniques. Indeed, S2 cells have been used over the last 10 y for the clinical development of vaccines, including a subunit vaccine targeting HER2-positive breast cancer, developed by Pharmexa A/S and currently in phase II clinical trials, and vaccines against dengue virus (Merck, Inc. 86 ) and West Nile virus (Hawai Biotech 87 ) currently in phase I development. Additionally, 2 malaria vaccines, from the Jenner Institute and Copenhagen University, respectively, are soon expected to enter phase I.…”

Section: Drosophilia S2 Cells: An Alternative Approach That Can Flymentioning

confidence: 99%

Non-conventional expression systems for the production of vaccine proteins and immunotherapeutic molecules

Legastelois

Buffin

Peubez

et al. 2016

Human Vaccines & Immunotherapeutics

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The increasing demand for recombinant vaccine antigens or immunotherapeutic molecules calls into question the universality of current protein expression systems. Vaccine production can require relatively low amounts of expressed materials, but represents an extremely diverse category consisting of different target antigens with marked structural differences. In contrast, monoclonal antibodies, by definition share key molecular characteristics and require a production system capable of very large outputs, which drives the quest for highly efficient and cost-effective systems. In discussing expression systems, the primary assumption is that a universal production platform for vaccines and immunotherapeutics will unlikely exist. This review provides an overview of the evolution of traditional expression systems, including mammalian cells, yeast and E.coli, but also alternative systems such as other bacteria than E. coli, transgenic animals, insect cells, plants and microalgae, Tetrahymena thermophila, Leishmania tarentolae, filamentous fungi, cell free systems, and the incorporation of non-natural amino acids.

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“…Two additional live attenuated tetravalent dengue vaccine candidates, TDV [30], sponsored by Takeda, and TV005 [31, 32], developed by the U.S. National Institutes of Health, are now close to entering clinical efficacy trials while other vaccine candidates are in various stages of early clinical and preclinical development using a variety of strategies including inactivated whole virus, recombinant constructs, DNA, virus vectors, and virus-like particles (VLPs) [33–36]. …”

Section: Evidence Of Immune-mediated Protection or Risk In Vaccine Stmentioning

confidence: 99%

Immune correlates for dengue vaccine development

Srikiatkhachorn

Yoon

2015

Expert Review of Vaccines

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Dengue virus is the leading cause of vector-borne viral disease with four serotypes in circulation. Vaccine development has been complicated by the potential for both protection and disease enhancement during heterologous infection. Secondary infection triggers cross-reactive immune memory responses which have varying functional and epitope specificities that determine protection or risk. Strongly neutralizing antibodies to quaternary epitopes may be especially important for virus neutralization. Cell-mediated immunity dominated by Th1 functions may also play an important role. Determining an immune correlate of protection or risk would be highly beneficial for vaccine development but is hampered by mechanistic uncertainties and assay limitations. Clinical efficacy trials and human infection models along with a systems approach may provide future opportunities to elucidate such correlates.

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Preclinical development of a dengue tetravalent recombinant subunit vaccine: Immunogenicity and protective efficacy in nonhuman primates

Cited by 65 publications

References 33 publications

T cell responses to nonstructural protein 3 distinguish infections by Dengue and Zika viruses

T cell responses to nonstructural protein 3 distinguish infections by Dengue and Zika viruses

Non-conventional expression systems for the production of vaccine proteins and immunotherapeutic molecules

Immune correlates for dengue vaccine development

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