scholarly journals Protective Immunity to Pseudomonas aeruginosa Induced with a Capsid-Modified Adenovirus Expressing P. aeruginosa OprF

2007 ◽  
Vol 81 (24) ◽  
pp. 13801-13808 ◽  
Author(s):  
Stefan Worgall ◽  
Anja Krause ◽  
JianPing Qiu ◽  
Ju Joh ◽  
Neil R. Hackett ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Wild Type ◽  
Cell Responses ◽  
Rgd Sequence ◽  
Hexon Protein ◽  
Repeat Administration ◽  
Antigen Presenting ◽  
Fiber Gene

ABSTRACT This study focuses on the development of a new clinical vaccine candidate (AdOprF.RGD.Epi8) against Pseudomonas aeruginosa using an E1− E3− adenovirus (Ad) vector expressing OprF (AdOprF.RGD.Epi8) and modifications of the Ad genome providing two capsid changes: (i) modification of the Ad hexon gene to incorporate an immune-dominant OprF epitope (Epi8) into loop 1 of the hexon, enabling repeat administration to boost the anti-OprF immune response, and (ii) modification of the fiber gene to incorporate an integrin-binding RGD sequence to enhance gene delivery to antigen-presenting cells. Western analysis confirmed that AdOprF.RGD.Epi8 expresses OprF, contains Epi8 in the hexon protein, and enhances gene transfer to dendritic cells compared to AdOprF, a comparable Ad vector expressing OprF with an unmodified capsid. Intramuscular immunization of C57BL/6 mice with AdOprF.RGD.Epi8 resulted in the generation of anti-OprF antibodies at comparable levels to those induced following immunization with AdOprF, but immunization with AdOprF.RGD.Epi8 was associated with increased CD4 and CD8 gamma interferon T-cell responses against OprF as well as increased survival against lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeat administration of AdOprF.RGD.Epi8 resulted in boosting of the humoral anti-OprF response as well as increased protection, whereas no boosting could be achieved with repeat administration of AdOprF. This suggests that the capsid-modified AdOprF.RGD.Epi8 vector is a more effective immunogen compared to a comparable wild-type Ad capsid, making it a good candidate for an anti-P. aeruginosa vaccine.

scholarly journals mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Susanne Rauch ◽  
Nicole Roth ◽  
Kim Schwendt ◽  
Mariola Fotin-Mleczek ◽  
Stefan O. Mueller ◽  
...  
Keyword(s):  
Viral Replication ◽  
Vaccine Candidate ◽  
Wild Type ◽  
Neutralising Antibodies ◽  
Cell Responses ◽  
Naturally Occurring ◽  
Safe Vaccine ◽  
Suboptimal Dose ◽  
Humoral Responses ◽  
Clinical Candidate

AbstractmRNA technologies have recently proven clinical efficacy against coronavirus disease 2019 and are among the most promising technologies to address the current pandemic. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle-encapsulated mRNA vaccine that encodes full-length, pre-fusion stabilised severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein. In contrast to previously published approaches, CVnCoV is exclusively composed of naturally occurring nucleotides. Immunisation with CVnCoV induced strong humoral responses with high titres of virus-neutralising antibodies and robust T-cell responses. CVnCoV vaccination protected hamsters from challenge with wild-type SARS-CoV-2, demonstrated by the absence of viral replication in the lungs. Hamsters vaccinated with a suboptimal dose of CVnCoV leading to breakthrough viral replication exhibited no evidence of vaccine-enhanced disease. Overall, data presented here provide evidence that CVnCoV represents a potent and safe vaccine candidate against SARS-CoV-2.

scholarly journals A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ren Yang ◽  
Yao Deng ◽  
Baoying Huang ◽  
Lei Huang ◽  
Ang Lin ◽  
...  
Keyword(s):  
Large Scale ◽  
Colloidal Stability ◽  
Vaccine Candidate ◽  
Vaccine Uptake ◽  
Core Shell ◽  
Wild Type ◽  
Cell Responses ◽  
Targeting Effect ◽  
Unique Core ◽  
Promising Vaccine Candidate

AbstractAlthough inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core–shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core–shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.

scholarly journals Influenza H1 Mosaic Hemagglutinin Vaccine Induces Broad Immunity and Protection in Mice

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 195 ◽  
Author(s):  
Brigette N. Corder ◽  
Brianna L. Bullard ◽  
Jennifer L. DeBeauchamp ◽  
Natalia A. Ilyushina ◽  
Richard J. Webby ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
Protective Immunity ◽  
Influenza A ◽  
T Cell Responses ◽  
Antibody Responses ◽  
T Cell Epitopes ◽  
Wild Type ◽  
Cell Responses ◽  
Universal Influenza Vaccine

Annually, influenza A virus (IAV) infects ~5–10% of adults and 20–30% of children worldwide. The primary resource to protect against infection is by vaccination. However, vaccination only induces strain-specific and transient immunity. Vaccine strategies that induce cross-protective immunity against the broad diversity of IAV are needed. Here we developed and tested a novel mosaic H1 HA immunogen. The mosaic immunogen was optimized in silico to include the most potential B and T cell epitopes (PBTE) across a diverse population of human H1 IAV. Phylogenetic analysis showed that the mosaic HA localizes towards the non-pandemic 2009 strains which encompasses the broadest diversity in the H1 IAV population. We compared the mosaic H1 immunogen to wild-type HA immunogens and the commercial inactivated influenza vaccine, Fluzone. When analyzed by ELISA, the mosaic immunogen induced stronger antibody responses against all four diverse H1 HA proteins. When analyzing T cell responses, again the mosaic immunogen induced stronger cellular immunity against all 4 diverse HA strains. Not only was the magnitude of T cell responses strongest in mosaic immunized mice, the number of epitopes recognized was also greater. The mosaic vaccinated mice showed strong cross-protection against challenges with three divergent IAV strains. These data show that the mosaic immunogen induces strong cross-protective immunity and should be investigated further as a universal influenza vaccine.

An Effective Live Vaccine Strain Of Trypanosoma Cruzi Prevents Chagas Disease In The Mouse Model

2020 ◽  
Author(s):  
Bijay Jha ◽  
Sanjay Varikuti ◽  
Nicholas Bishop ◽  
Gregory dos Santos ◽  
Jacquelyn McDonald ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Vaccine Candidate ◽  
Etiologic Agent ◽  
Live Vaccine ◽  
Parasite Line ◽  
Wild Type ◽  
Knock Out ◽  
Cell Responses ◽  
Deficient Mice

Abstract Trypanosoma cruzi is the etiologic agent of Chagas disease for which there are no prophylactic vaccines. Cyclophilin 19 is a secreted cis-trans peptidyl isomerase expressed in all life stages of Trypanosoma cruzi, which in the insect stage leads to the inactivation of insect anti-parasitic peptides and parasite transformation and in intracellular amastigotes participates in generating ROS enhancing parasite growth. We have generated a parasite knock-out mutant of Cyp19 which fails to replicate in cell culture or in mice indicating that lack of Cyp19 is critical for infectivity. Knock-out parasites fail to replicate in or cause clinical disease in immune-deficient mice further validating their lack of virulence. Repeated inoculation of knock-out parasites into immuno-competent mice elicits parasite-specific antibodies and T-cell responses. Challenge of immunized mice with wild-type parasites is 100% effective at preventing disease. These results indicate that the knock-out parasite line is a live vaccine candidate for Chagas disease.

scholarly journals Protective Immunity in Macaques Vaccinated with a Modified Vaccinia Virus Ankara-Based Measles Virus Vaccine in the Presence of Passively Acquired Antibodies

2000 ◽  
Vol 74 (9) ◽  
pp. 4236-4243 ◽  
Author(s):  
Koert J. Stittelaar ◽  
Linda S. Wyatt ◽  
Rik L. de Swart ◽  
Helma W. Vos ◽  
Jan Groen ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Measles Virus ◽  
Wild Type ◽  
Live Attenuated Vaccine ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Current Vaccine ◽  
Induced Immunity

ABSTRACT Recombinant modified vaccinia virus Ankara (MVA), encoding the measles virus (MV) fusion (F) and hemagglutinin (H) (MVA-FH) glycoproteins, was evaluated in an MV vaccination-challenge model with macaques. Animals were vaccinated twice in the absence or presence of passively transferred MV-neutralizing macaque antibodies and challenged 1 year later intratracheally with wild-type MV. After the second vaccination with MVA-FH, all the animals developed MV-neutralizing antibodies and MV-specific T-cell responses. Although MVA-FH was slightly less effective in inducing MV-neutralizing antibodies in the absence of passively transferred antibodies than the currently used live attenuated vaccine, it proved to be more effective in the presence of such antibodies. All vaccinated animals were effectively protected from the challenge infection. These data suggest that MVA-FH should be further tested as an alternative to the current vaccine for infants with maternally acquired MV-neutralizing antibodies and for adults with waning vaccine-induced immunity.

scholarly journals Particulate Mycobacterial Vaccines Induce Protective Immunity against Tuberculosis in Mice

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2060
Author(s):  
Shuxiong Chen ◽  
Diana H. Quan ◽  
Xiaonan T. Wang ◽  
Sarah Sandford ◽  
Joanna R. Kirman ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
High Yield ◽  
Mycobacterial Antigen ◽  
Bacillus Calmette Guerin ◽  
Cell Responses ◽  
Particulate Form ◽  
Production Strain

Currently available vaccines fail to provide consistent protection against tuberculosis (TB). New, improved vaccines are urgently needed for controlling the disease. The mycobacterial antigen fusions H4 (Ag85B-TB10.4) and H28 (Ag85B-TB10.4-Rv2660c) have been shown to be very immunogenic and have been considered as potential candidates for TB vaccine development. However, soluble protein vaccines are often poorly immunogenic, but augmented immune responses can be induced when selected antigens are delivered in particulate form. This study investigated whether the mycobacterial antigen fusions H4 and H28 can induce protective immunity when assembled into particulate vaccines (polyester nanoparticle-H4, polyester nanoparticle-H28, H4 nanoparticles and H28 nanoparticles). The particulate mycobacterial vaccines were assembled inside an engineered endotoxin-free production strain of Escherichia coli at high yield. Vaccine nanoparticles were purified and induced long-lasting antigen-specific T cell responses and protective immunity in mice challenged by aerosol with virulent Mycobacterium tuberculosis. A significant reduction of M. tuberculosis CFU, up to 0.7-log10 protection, occurred in the lungs of mice immunized with particulate vaccines in comparison to placebo-vaccinated mice (p < 0.0001). Polyester nanoparticles displaying the mycobacterial antigen fusion H4 induced a similar level of protective immunity in the lung when compared to M. bovis bacillus Calmette-Guérin (BCG), the currently approved TB vaccine. The safe and immunogenic polyester nanoparticle-H4 vaccine is a promising subunit vaccine candidate, as it can be cost-effectively manufactured and efficiently induces protection against TB.

scholarly journals An adjuvanted subunit SARS-CoV-2 spike protein vaccine provides protection against Covid-19 infection and transmission

2021 ◽  
Author(s):  
Kairat Tabynov ◽  
Nurkeldi Turebekov ◽  
Meruert Babayeva ◽  
Gleb Fomin ◽  
Toktasyn Yerubaev ◽  
...  
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
T Cell Responses ◽  
Spike Protein ◽  
Effective Vaccine ◽  
Protein Vaccine ◽  
Wild Type ◽  
Cell Responses ◽  
Ongoing Development

Abstract Recombinant protein approaches offer major promise for safe and effective vaccine prevention of SARS-CoV-2 infection. We developed a recombinant spike protein vaccine (called NARUVAX-C19) and characterized its ability when formulated with a nanoemulsion adjuvant to induce anti-spike antibody and T-cell responses and provide protection including against viral transmission in rodent. In mice, NARUVAX-C19 vaccine administered intramuscularly twice at 21-day interval elicited balanced Th1/Th2 humoral and T-cell responses with high titers of neutralizing antibodies against wild-type (D614G) and delta (B.1.617.2) variants. In Syrian hamsters, NARUVAX-C19 provided complete protection against wild-type (D614G) infection and prevented its transmission to naïve animals placed in the same cage as challenged animals. The results contrasted with only weak protection seen with a monomeric spike receptor binding domain (RBD) vaccine even when formulated with the same adjuvant. These encouraging results warrant ongoing development of this Covid-19 vaccine candidate.

scholarly journals Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

2021 ◽  
Vol 7 (22) ◽  
pp. eabg7156
Author(s):  
So-Hee Hong ◽  
Hanseul Oh ◽  
Yong Wook Park ◽  
Hye Won Kwak ◽  
Eun Young Oh ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
Statistical Significance ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Vaccine Candidates ◽  
Cell Responses ◽  
Antibody Levels ◽  
Further Development

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

Sign in / Sign up

Export Citation Format

Share Document