scholarly journals A Measles Virus-Based Vaccine Candidate Mediates Protection against Zika Virus in an Allogeneic Mouse Pregnancy Model

2018 ◽  
Vol 93 (3) ◽  
Author(s):  
Cindy Nürnberger ◽  
Bianca S. Bodmer ◽  
Anna H. Fiedler ◽  
Gülsah Gabriel ◽  
Michael D. Mühlebach
Keyword(s):  
Immune Responses ◽  
Vaccine Strain ◽  
Zika Virus ◽  
Measles Virus ◽  
Vaccine Candidate ◽  
Vaccine Platform ◽  
Cellular Immune Responses ◽  
E Protein ◽  
Cellular Immune ◽  
The Impact

ABSTRACTThe impact of the Zika virus (ZIKV) epidemic highlights the need for vaccines that reduce or prevent infection and reliably prevent teratogenic complications. The live-attenuated measles virus (MV) vaccine strains are a promising vaccine platform, since they induce robust humoral and cellular immune responses against additional antigens and have an excellent safety record. To explore its potential to protect against ZIKV, we compared a recombinant Schwarz strain MV that encodes ZIKV prM and soluble E proteins (MV-Zika-sE) with a prototypic alum-adjuvanted whole inactivated ZIKV particle vaccine. Analysis of MV-Zika-sE-infected cells confirmed antigen expression, and the virus replicated with vaccine strain characteristics. Immunized IFNAR−/−-CD46Ge mice developed E protein-specific and neutralizing antibodies, and ZIKV E-specific cellular immune responses were observed by gamma interferon (IFN-γ) enzyme-linked immunospot (ELISpot) andin vitroT cell proliferation assays. To analyze protective efficacy, vaccinated female mice were challenged with ZIKV after allogeneic mating. In MV-Zika-sE-vaccinated mice, weight gain was similar to that in uninfected mice, while no plasma viremia was detectable in the majority of the animals. In contrast, infected control animals gained less weight and experienced about 100-fold higher viremia over at least 3 days. Moreover, vaccination with MV-Zika-sE reduced the ZIKV load in different organs and the placentas and prevented infection of the fetus. Consequently, no fetal growth retardation, anemia, or death due to ZIKV infection was seen in MV-Zika-sE-vaccinated dams. In contrast, the inactivated ZIKV vaccine had little to no effect in our studies. Therefore, the MV-derived ZIKV vaccine is a promising candidate for further preclinical and clinical development.IMPORTANCEZika virus (ZIKV) is a mosquito-borne flavivirus that causes a variety of neurological complications, including congenital birth defects. Despite the urgent need, no ZIKV vaccine has yet been licensed. Recombinant vaccine strain-derived measles viruses (MV) constitute a promising vector platform to induce immunity against foreign pathogens by expressing antigens from additional transcription units while at the same time possessing a remarkable safety profile. This concept has already been validated against different pathogens, including at least 3 other flaviviruses, and our data show that vaccination with MV expressing soluble ZIKV E protein significantly diminishes infection and prevents fetal loss or damage in an allogeneic mouse pregnancy model. It can thus be regarded as a promising emergency vaccine candidate with the potential for inclusion in routine vaccination settings in areas of endemicity to prevent teratogenic effects of circulating ZIKV during pregnancy, comparable to standard rubella virus vaccination.

scholarly journals Induction of Broad-Based Immunity and Protective Efficacy by Self-amplifying mRNA Vaccines Encoding Influenza Virus Hemagglutinin

2015 ◽  
Vol 90 (1) ◽  
pp. 332-344 ◽  
Author(s):  
Michela Brazzoli ◽  
Diletta Magini ◽  
Alessandra Bonci ◽  
Scilla Buccato ◽  
Cinzia Giovani ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Immune Responses ◽  
Upper Respiratory Tract ◽  
Vaccine Platform ◽  
Major Health Problem ◽  
Cellular Immune Responses ◽  
Influenza Virus Hemagglutinin ◽  
Cellular Immune ◽  
The Impact

ABSTRACTSeasonal influenza is a vaccine-preventable disease that remains a major health problem worldwide, especially in immunocompromised populations. The impact of influenza disease is even greater when strains drift, and influenza pandemics can result when animal-derived influenza virus strains combine with seasonal strains. In this study, we used the SAM technology and characterized the immunogenicity and efficacy of a self-amplifying mRNA expressing influenza virus hemagglutinin (HA) antigen [SAM(HA)] formulated with a novel oil-in-water cationic nanoemulsion. We demonstrated that SAM(HA) was immunogenic in ferrets and facilitated containment of viral replication in the upper respiratory tract of influenza virus-infected animals. In mice, SAM(HA) induced potent functional neutralizing antibody and cellular immune responses, characterized by HA-specific CD4 T helper 1 and CD8 cytotoxic T cells. Furthermore, mice immunized with SAM(HA) derived from the influenza A virus A/California/7/2009 (H1N1) strain (Cal) were protected from a lethal challenge with the heterologous mouse-adapted A/PR/8/1934 (H1N1) virus strain (PR8). Sera derived from SAM(H1-Cal)-immunized animals were not cross-reactive with the PR8 virus, whereas cross-reactivity was observed for HA-specific CD4 and CD8 T cells. Finally, depletion of T cells demonstrated that T-cell responses were essential in mediating heterologous protection. If the SAM vaccine platform proves safe, well tolerated, and effective in humans, the fully synthetic SAM vaccine technology could provide a rapid response platform to control pandemic influenza.IMPORTANCEIn this study, we describe protective immune responses in mice and ferrets after vaccination with a novel HA-based influenza vaccine. This novel type of vaccine elicits both humoral and cellular immune responses. Although vaccine-specific antibodies are the key players in mediating protection from homologous influenza virus infections, vaccine-specific T cells contribute to the control of heterologous infections. The rapid production capacity and the synthetic origin of the vaccine antigen make the SAM platform particularly exploitable in case of influenza pandemic.

scholarly journals Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform

2020 ◽  
Author(s):  
Flavia Chiuppesi ◽  
Marcela d’Alincourt Salazar ◽  
Heidi Contreras ◽  
Vu Nguyen ◽  
Joy Martinez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Vaccine Platform ◽  
Synthetic Dna ◽  
Cellular Immune Responses ◽  
Global Pandemic ◽  
Immunodominant Antigens ◽  
Cellular Immune

Abstract Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

scholarly journals Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Flavia Chiuppesi ◽  
Marcela d’Alincourt Salazar ◽  
Heidi Contreras ◽  
Vu H. Nguyen ◽  
Joy Martinez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Vaccine Platform ◽  
Synthetic Dna ◽  
Cellular Immune Responses ◽  
Global Pandemic ◽  
Immunodominant Antigens ◽  
Cellular Immune

AbstractModified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We demonstrate the construction of a vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we use this vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. We show that mice immunized with these sMVA vectors develop robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

scholarly journals Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

2020 ◽  
Author(s):  
Flavia Chiuppesi ◽  
Marcela d’Alincourt Salazar ◽  
Heidi Contreras ◽  
Vu H Nguyen ◽  
Joy Martinez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Vaccine Platform ◽  
Synthetic Dna ◽  
Cellular Immune Responses ◽  
Global Pandemic ◽  
Immunodominant Antigens ◽  
Cellular Immune

AbstractModified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

scholarly journals mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Helen Parry ◽  
Gokhan Tut ◽  
Rachel Bruton ◽  
Sian Faustini ◽  
Christine Stephens ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cellular Response ◽  
Humoral Response ◽  
Antibody Responses ◽  
Vaccine Platform ◽  
Humoral Immune ◽  
Vaccine Responses ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

scholarly journals VLP-Based COVID-19 Vaccines: An Adaptable Technology against the Threat of New Variants

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1409
Author(s):  
Wasim A. Prates-Syed ◽  
Lorena C. S. Chaves ◽  
Karin P. Crema ◽  
Larissa Vuitika ◽  
Aline Lira ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Convergent Evolution ◽  
Vaccine Development ◽  
Receptor Binding Domain ◽  
Vaccine Platform ◽  
Cellular Immune Responses ◽  
Alpha Beta ◽  
Cellular Immune ◽  
Financial Losses

Virus-like particles (VLPs) are a versatile, safe, and highly immunogenic vaccine platform. Recently, there are developmental vaccines targeting SARS-CoV-2, the causative agent of COVID-19. The COVID-19 pandemic affected humanity worldwide, bringing out incomputable human and financial losses. The race for better, more efficacious vaccines is happening almost simultaneously as the virus increasingly produces variants of concern (VOCs). The VOCs Alpha, Beta, Gamma, and Delta share common mutations mainly in the spike receptor-binding domain (RBD), demonstrating convergent evolution, associated with increased transmissibility and immune evasion. Thus, the identification and understanding of these mutations is crucial for the production of new, optimized vaccines. The use of a very flexible vaccine platform in COVID-19 vaccine development is an important feature that cannot be ignored. Incorporating the spike protein and its variations into VLP vaccines is a desirable strategy as the morphology and size of VLPs allows for better presentation of several different antigens. Furthermore, VLPs elicit robust humoral and cellular immune responses, which are safe, and have been studied not only against SARS-CoV-2 but against other coronaviruses as well. Here, we describe the recent advances and improvements in vaccine development using VLP technology.

scholarly journals Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 125 ◽  
Author(s):  
Entao Li ◽  
Feihu Yan ◽  
Pei Huang ◽  
Hang Chi ◽  
Shengnan Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Rabies Virus ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Viral Vector ◽  
Vaccine Vector ◽  
Vaccine Candidates ◽  
Cellular Immune Responses ◽  
Cellular Immune

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.

scholarly journals Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice

2017 ◽  
Vol 91 (12) ◽  
Author(s):  
Shiliang A. Liu ◽  
Brent A. Stanfield ◽  
Vladimir N. Chouljenko ◽  
Shan Naidu ◽  
Ingeborg Langohr ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Strain ◽  
Equine Herpesvirus ◽  
Herpes Simplex Virus 1 ◽  
Equine Herpesvirus 1 ◽  
Cellular Immune Responses ◽  
Herpesvirus 1 ◽  
Simplex Virus ◽  
Cellular Immune ◽  
Hsv 1

ABSTRACT Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the live-attenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses. The VC2–EHV-1–gD recombinant virus was constructed by inserting an EHV-1 gD expression cassette under the control of the cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV-1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through intramuscular injection. Vaccination with both the VC2–EHV-1–gD vaccine and the commercially available vaccine Vetera EHVXP 1/4 (Vetera; Boehringer Ingelheim Vetmedica) resulted in the production of neutralizing antibodies, the levels of which were significantly higher in comparison to those in VC2- and mock-vaccinated animals (P < 0.01 or P < 0.001). Analysis of EHV-1-reactive IgG subtypes demonstrated that vaccination with the VC2–EHV-1–gD vaccine stimulated robust IgG1 and IgG2a antibodies after three vaccinations (P < 0.001). Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM than mice in the other groups before and after challenge (P < 0.01 or P < 0.05). Vaccination with VC2–EHV-1–gD stimulated strong cellular immune responses, characterized by the upregulation of both interferon- and tumor necrosis factor-positive CD4+ T cells and CD8+ T cells. Overall, the data suggest that the HSV-1 VC2 vaccine strain may be used as a viral vector for the vaccination of horses as well as, potentially, for the vaccination of other economically important animals. IMPORTANCE A novel virus-vectored VC2–EHV-1–gD vaccine was constructed using the live-attenuated HSV-1 VC2 vaccine strain. This vaccine stimulated strong humoral and cellular immune responses in mice, suggesting that it could protect horses against EHV-1 infection.

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