Subunit vaccine formulations based on recombinant envelope proteins of Chikungunya virus elicit balanced Th1/Th2 response and virus-neutralizing antibodies in mice

Epstein–Barr virus (EBV) is the primary cause of infectious mononucleosis and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. EBV core fusion machinery envelope proteins gH/gL and gB coordinately mediate EBV fusion and entry into its target cells, B lymphocytes and epithelial cells, suggesting these proteins could induce antibodies that prevent EBV infection. We previously reported that the immunization of rabbits with recombinant EBV gH/gL or trimeric gB each induced markedly higher serum EBV-neutralizing titers for B lymphocytes than that of the leading EBV vaccine candidate gp350. In this study, we demonstrated that immunization of rabbits with EBV core fusion machinery proteins induced high titer EBV neutralizing antibodies for both B lymphocytes and epithelial cells, and EBV gH/gL in combination with EBV trimeric gB elicited strong synergistic EBV neutralizing activities. Furthermore, the immune sera from rabbits immunized with EBV gH/gL or trimeric gB demonstrated strong passive immune protection of humanized mice from lethal dose EBV challenge, partially or completely prevented death respectively, and markedly decreased the EBV load in peripheral blood of humanized mice. These data strongly suggest the combination of EBV core fusion machinery envelope proteins gH/gL and trimeric gB is a promising EBV prophylactic vaccine.

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A Novel E2 Glycoprotein Subunit Marker Vaccine Produced in Plant Is Able to Prevent Classical Swine Fever Virus Vertical Transmission after Double Vaccination

Vaccines ◽

10.3390/vaccines9050418 ◽

2021 ◽

Vol 9 (5) ◽

pp. 418

Author(s):

Youngmin Park ◽

Yeonsu Oh ◽

Miaomiao Wang ◽

Llilianne Ganges ◽

José Alejandro Bohórquez ◽

...

Keyword(s):

Vertical Transmission ◽

Classical Swine Fever Virus ◽

Neutralizing Antibodies ◽

Subunit Vaccine ◽

Vaccine Dose ◽

Classical Swine Fever ◽

Fever Virus ◽

Tissue Samples ◽

Marker Vaccine ◽

E2 Glycoprotein

The efficacy of a novel subunit vaccine candidate, based in the CSFV E2 glycoprotein produced in plants to prevent classical swine fever virus (CSFV) vertical transmission, was evaluated. A Nicotiana benthamiana tissue culture system was used to obtain a stable production of the E2-glycoprotein fused to the porcine Fc region of IgG. Ten pregnant sows were divided into three groups: Groups 1 and 2 (four sows each) were vaccinated with either 100 μg/dose or 300 μg/dose of the subunit vaccine at 64 days of pregnancy. Group 3 (two sows) was injected with PBS. Groups 1 and 2 were boosted with the same vaccine dose. At 10 days post second vaccination, the sows in Groups 2 and 3 were challenged with a highly virulent CSFV strain. The vaccinated sows remained clinically healthy and seroconverted rapidly, showing efficient neutralizing antibodies. The fetuses from vaccinated sows did not show gross lesions, and all analyzed tissue samples tested negative for CSFV replication. However, fetuses of non-vaccinated sows had high CSFV replication in tested tissue samples. The results suggested that in vaccinated sows, the plant produced E2 marker vaccine induced the protective immunogenicity at challenge, leading to protection from vertical transmission to fetuses.

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Induction of mucosal immunity and protection by intranasal immunization with a respiratory syncytial virus subunit vaccine formulation

Journal of General Virology ◽

10.1099/vir.0.058461-0 ◽

2014 ◽

Vol 95 (2) ◽

pp. 301-306 ◽

Cited By ~ 31

Author(s):

R. Garg ◽

L. Latimer ◽

E. Simko ◽

V. Gerdts ◽

A. Potter ◽

...

Keyword(s):

T Cells ◽

Respiratory Syncytial Virus ◽

Lymph Nodes ◽

Neutralizing Antibodies ◽

Subunit Vaccine ◽

Affinity Maturation ◽

Protein Formulation ◽

Cross Presentation ◽

Mucosal Surfaces ◽

Syncytial Virus

The majority of infections, including those caused by respiratory syncytial virus (RSV), occur at mucosal surfaces. As no RSV vaccine is available our goal is to produce an effective subunit vaccine with an adjuvant suitable for mucosal delivery and cross-presentation. A truncated secreted version of the RSV fusion (ΔF) protein formulated with polyI : C, an innate defence regulator peptide and polyphosphazene, induced local and systemic immunity, including affinity maturation of RSV F-specific IgG, IgA and virus-neutralizing antibodies, and F-specific CD8+ T-cells in the lung, when delivered intranasally. Furthermore, this ΔF protein formulation promoted the production of CD8+ central memory T-cells in the mediastinal lymph nodes and provided protection from RSV challenge. Formulation of ΔF protein with this adjuvant combination enhanced uptake by lung dendritic cells and trafficking to the draining lymph nodes. The ΔF protein formulation was confirmed to be highly efficacious and safe in cotton rats.

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A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in non-human primates

10.1101/2021.07.13.452251 ◽

2021 ◽

Author(s):

Neil C Dalvie ◽

Lisa H Tostanoski ◽

Sergio A Rodriguez-Aponte ◽

Kawaljit Kaur ◽

Sakshi Bajoria ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Cellular Response ◽

Subunit Vaccine ◽

Hepatitis B Surface Antigen ◽

Low Cost ◽

Humoral Response ◽

High Volume ◽

Developed Countries ◽

Protein Subunit ◽

Middle Income

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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LT-IIb(T13I), a Non-Toxic Type II Heat-Labile Enterotoxin, Augments the Capacity of a Ricin Toxin Subunit Vaccine to Evoke Neutralizing Antibodies and Protective Immunity

PLoS ONE ◽

10.1371/journal.pone.0069678 ◽

2013 ◽

Vol 8 (8) ◽

pp. e69678 ◽

Cited By ~ 12

Author(s):

Christopher J. Greene ◽

Chrystal M. Chadwick ◽

Lorrie M. Mandell ◽

John C. Hu ◽

Joanne M. O’Hara ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Protective Immunity ◽

Subunit Vaccine ◽

Type Ii ◽

Ricin Toxin ◽

Heat Labile

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Serological Responses in Patients Infected with Mayaro Virus and Evaluation of Cross-Protective Responses against Chikungunya Virus

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.21-0579 ◽

2021 ◽

Author(s):

Nathen E. Bopp ◽

Kara J. Jencks ◽

Crystyan Siles ◽

Carolina Guevara ◽

Stalin Vilcarromero ◽

...

Keyword(s):

Latin America ◽

South America ◽

Neutralizing Antibodies ◽

Chikungunya Virus ◽

Neutralization Test ◽

Close Relative ◽

Previous Exposure ◽

Chikv Infection ◽

The Caribbean ◽

Mayaro Virus

Mayaro virus (MAYV) is an alphavirus endemic to both Latin America and the Caribbean. Recent reports have questioned the ability of MAYV and its close relative, Chikungunya virus (CHIKV), to generate cross-reactive, neutralizing antibodies to one another. Since CHIKV was introduced to South America in 2013, discerning whether individuals have cross-reactive antibodies or whether they have had exposures to both viruses previously has been difficult. Using samples obtained from people infected with MAYV prior to the introduction of CHIKV in the Americas, we performed neutralizing assays and observed no discernable neutralization of CHIKV by sera from patients previously infected with MAYV. These data suggest that a positive CHIKV neutralization test cannot be attributed to prior exposure to MAYV and that previous exposure to MAYV may not be protective against a subsequent CHIKV infection.

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Evaluation of A Baculovirus-Expressed VP2 Subunit Vaccine for the Protection of White-Tailed Deer (Odocoileus virginianus) from Epizootic Hemorrhagic Disease

Vaccines ◽

10.3390/vaccines8010059 ◽

2020 ◽

Vol 8 (1) ◽

pp. 59

Author(s):

Sun Young Sunwoo ◽

Leela E. Noronha ◽

Igor Morozov ◽

Jessie D. Trujillo ◽

In Joong Kim ◽

...

Keyword(s):

North America ◽

Neutralizing Antibodies ◽

Subunit Vaccine ◽

Rna Virus ◽

Expression System ◽

Clinical Disease ◽

Vascular Lesions ◽

Hemorrhagic Disease ◽

Epizootic Hemorrhagic Disease ◽

Homologous Virus

Epizootic hemorrhagic disease virus (EHDV) is an arthropod-transmitted RNA virus and the causative agent of epizootic hemorrhagic disease (EHD) in wild and domestic ruminants. In North America, white-tailed deer (WTD) experience the highest EHD-related morbidity and mortality, although clinical disease is reported in cattle during severe epizootics. No commercially licensed EHDV vaccine is available in North America. The objective of this study was to develop and evaluate a subunit vaccine candidate to control EHD in WTD. Recombinant VP2 (rVP2) outer capsid proteins of EHDV serotypes 2 (EHDV-2) and 6 (EHDV-6) were produced in a baculovirus-expression system. Mice and cattle vaccinated with EHDV-2 or EHDV-6 rVP2 produced homologous virus-neutralizing antibodies. In an immunogenicity/efficacy study, captive-bred WTD received 2 doses of EHDV-2 rVP2 or sham vaccine, then were challenged with wild-type EHDV-2 at 30 d post vaccination. None of the rVP2-vaccinated deer developed clinical disease, no viral RNA was detected in their blood or tissues (liver, lung, spleen, kidney), and no EHDV-induced lesions were observed. Sham-vaccinated deer developed clinical disease with viremia and typical EHD vascular lesions. Here, we demonstrate a rVP2 subunit vaccine that can provide protective immunity from EHDV infection and which may serve as an effective tool in preventing clinical EHD and reducing virus transmission.

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A Hepatitis C Virus DNA Vaccine Encoding a Secreted, Oligomerized Form of Envelope Proteins Is Highly Immunogenic and Elicits Neutralizing Antibodies in Vaccinated Mice

Frontiers in Immunology ◽

10.3389/fimmu.2019.01145 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 8

Author(s):

Makutiro Ghislain Masavuli ◽

Danushka K. Wijesundara ◽

Alexander Underwood ◽

Dale Christiansen ◽

Linda Earnest-Silveira ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Dna Vaccine ◽

Neutralizing Antibodies ◽

Envelope Proteins

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Effects of Chikungunya virus immunity on Mayaro virus disease and epidemic potential

Scientific Reports ◽

10.1038/s41598-019-56551-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 9

Author(s):

Emily M. Webb ◽

Sasha R. Azar ◽

Sherry L. Haller ◽

Rose M. Langsjoen ◽

Candace E. Cuthbert ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Chikungunya Virus ◽

Semliki Forest Virus ◽

Virus Disease ◽

Cross Protection ◽

Health Concern ◽

Antigenic Relationship ◽

Wild Type ◽

Chikv Infection ◽

Mayaro Virus

AbstractMayaro virus (MAYV) causes an acute febrile illness similar to that produced by chikungunya virus (CHIKV), an evolutionary relative in the Semliki Forest virus complex of alphaviruses. MAYV emergence is typically sporadic, but recent isolations and outbreaks indicate that the virus remains a public health concern. Given the close phylogenetic and antigenic relationship between CHIKV and MAYV, and widespread distribution of CHIKV, we hypothesized that prior CHIKV immunity may affect MAYV pathogenesis and/or influence its emergence potential. We pre-exposed immunocompetent C57BL/6 and immunocompromised A129 or IFNAR mice to wild-type CHIKV, two CHIKV vaccines, or a live-attenuated MAYV vaccine, and challenged with MAYV. We observed strong cross-protection against MAYV for mice pre-exposed to wild-type CHIKV, and moderately but significantly reduced cross-protection from CHIKV-vaccinated animals. Immunity to other alphavirus or flavivirus controls provided no protection against MAYV disease or viremia. Mechanistic studies suggested that neutralizing antibodies alone can mediate this protection, with T-cells having no significant effect on diminishing disease. Finally, human sera obtained from naturally acquired CHIKV infection cross-neutralized MAYV at high titers in vitro. Altogether, our data suggest that CHIKV infection can confer cross-protective effects against MAYV, and the resultant reduction in viremia may limit the emergence potential of MAYV.

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