Plant-produced YFE-1T subunit vaccine against Yellow Fever induces humoral response in captive golden-headed lion tamarin (Leontopithecus chrysomelas)

Vaccines against SARS-CoV-2 have been distributed at massive scale in developed countries, and have been effective at preventing COVID-19. Access to vaccines is limited, however, in low- and middle-income countries (LMICs) due to insufficient supply, high costs, and cold storage requirements. New vaccines that can be produced in existing manufacturing facilities in LMICs, can be manufactured at low cost, and use widely available, proven, safe adjuvants like alum, would improve global immunity against SARS-CoV-2. One such protein subunit vaccine is produced by the Serum Institute of India Pvt. Ltd. and is currently in clinical testing. Two protein components, the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen virus-like particles (VLPs), are each produced in yeast, which would enable a low-cost, high-volume manufacturing process. Here, we describe the design and preclinical testing of the RBD-VLP vaccine in cynomolgus macaques. We observed titers of neutralizing antibodies (>104) above the range of protection for other licensed vaccines in non-human primates. Interestingly, addition of a second adjuvant (CpG1018) appeared to improve the cellular response while reducing the humoral response. We challenged animals with SARS-CoV-2, and observed a ~3.4 and ~2.9 log10 reduction in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, compared to sham controls. These results inform the design and formulation of current clinical COVID-19 vaccine candidates like the one described here, and future designs of RBD-based vaccines against variants of SARS-CoV-2 or other betacoronaviruses.

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Spontaneous meningoencephalitis by Staphylococcus aureus in an infant golden‐headed lion tamarin ( Leontopithecus chrysomelas )

Journal of Medical Primatology ◽

10.1111/jmp.12436 ◽

2019 ◽

Vol 48 (6) ◽

pp. 370-373

Author(s):

Camila V. Molina ◽

Marina G. Bueno ◽

Maria Cecília M. Kierulff ◽

Alcides Pissinatti ◽

Marcos P. V. Cunha ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Leontopithecus Chrysomelas ◽

Lion Tamarin

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Do Habitat Use and Interspecific Association Reflect Predation Risk for the Golden-Headed Lion Tamarin (Leontopithecus chrysomelas)?

International Journal of Primatology ◽

10.1007/s10764-015-9885-6 ◽

2015 ◽

Vol 36 (6) ◽

pp. 1198-1215 ◽

Cited By ~ 2

Author(s):

Juliana Monteiro de Almeida Rocha ◽

Kristel Myriam De Vleeschouwer ◽

Paula Pedreira Reis ◽

Carlos Eduardo de V. Grelle ◽

Leonardo C. Oliveira

Keyword(s):

Habitat Use ◽

Predation Risk ◽

Interspecific Association ◽

Leontopithecus Chrysomelas ◽

Lion Tamarin

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Geographic Distribution of the Golden-Headed Lion Tamarin, Leontopithecus chrysomelas: Implications for Its Management and Conservation

Folia Primatologica ◽

10.1159/000157244 ◽

1997 ◽

Vol 68 (3-5) ◽

pp. 161-180 ◽

Cited By ~ 24

Author(s):

Luiz Paulo de S. Pinto ◽

Anthony B. Rylands

Keyword(s):

Geographic Distribution ◽

Leontopithecus Chrysomelas ◽

Lion Tamarin ◽

Management And Conservation

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Identifying and Prioritizing Forest Patches Key for the Survival of the Golden-Headed Lion Tamarin (Leontopithecus chrysomelas)

Neotropical Primates ◽

10.1896/044.019.0105 ◽

2012 ◽

Vol 19 (1) ◽

pp. 28-33 ◽

Cited By ~ 1

Author(s):

Sara L. Zeigler

Keyword(s):

Forest Patches ◽

Leontopithecus Chrysomelas ◽

Lion Tamarin

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Activation of an Effective Immune Response after Yellow Fever Vaccination Is Associated with the Genetic Background and Early Response of IFN-γ and CLEC5A

Viruses ◽

10.3390/v13010096 ◽

2021 ◽

Vol 13 (1) ◽

pp. 96

Author(s):

Tamiris Azamor ◽

Andréa Marques Vieira da Silva ◽

Juliana Gil Melgaço ◽

Ana Paula dos Santos ◽

Caroline Xavier-Carvalho ◽

...

Keyword(s):

Yellow Fever ◽

Neutralizing Antibodies ◽

Humoral Response ◽

Early Response ◽

Yellow Fever Vaccine ◽

Nucleotide Polymorphisms ◽

Lectin Domain ◽

Ifn Γ ◽

Innate Antiviral Response ◽

Cellular Phenotypes

The yellow fever vaccine (YF17DD) is highly effective with a single injection conferring protection for at least 10 years. The YF17DD induces polyvalent responses, with a TH1/TH2 CD4+ profile, robust T CD8+ responses, and synthesis of interferon-gamma (IFN-γ), culminating in high titers of neutralizing antibodies. Furthermore, C-type lectin domain containing 5A (CLEC5A) has been implicated in innate outcomes in other flaviviral infections. Here, we conducted a follow-up study in volunteers immunized with YF17DD, investigating the humoral response, cellular phenotypes, gene expression, and single nucleotide polymorphisms (SNPs) of IFNG and CLEC5A, to clarify the role of these factors in early response after vaccination. Activation of CLEC5A+ monocytes occurred five days after vaccination (DAV). Following, seven DAV data showed activation of CD4+ and CD8+T cells together with early positive correlations between type II IFN and genes of innate antiviral response (STAT1, STAT2, IRF7, IRF9, OAS1, and RNASEL) as well as antibody levels. Furthermore, individuals with genotypes rs2430561 AT/AA, rs2069718 AG/AA (IFNG), and rs13237944 AC/AA (CLEC5A), exhibited higher expression of IFNG and CLEC5A, respectively. Together, we demonstrated that early IFN-γ and CLEC5A responses, associated with rs2430561, rs2069718, and rs13237944 genotypes, may be key mechanisms in the long-lasting immunity elicited by YF17DD.

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Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine

10.1101/2020.12.18.423552 ◽

2020 ◽

Author(s):

Yangtao Wu ◽

Xiaofen Huang ◽

Lunzhi Yuan ◽

Shaojuan Wang ◽

Yali Zhang ◽

...

Keyword(s):

T Cell ◽

Subunit Vaccine ◽

Vaccine Candidate ◽

Protective Efficacy ◽

Humoral Response ◽

Neutralizing Antibody ◽

Cell Immune Response ◽

Antibody Titers ◽

A Subunit ◽

Sterilizing Immunity

AbstractA safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.

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