Distribution and absence of generalized lesions in mice following single dose intramuscular inoculation of the vaccine candidate MVA-MERS-S

At present, concerns that the recent global emergence of SARS-CoV-2 variants could compromise the current vaccines have been raised, highlighting the urgent demand for new vaccines capable of eliciting T cell-mediated immune responses, as well as B cell-mediated neutralizing antibody production. In this study, we developed a novel recombinant Mycobacterium paragordonae expressing the SARS-CoV-2 receptor-binding domain (RBD) (rMpg-RBD-7) that is capable of eliciting RBD-specific immune responses in vaccinated mice. The potential use of rMpg-RBD-7 as a vaccine for SARS-CoV-2 infections was evaluated in in vivo using mouse models of two different modules, one for single-dose vaccination and the other for two-dose vaccination. In a single-dose vaccination model, we found that rMpg-RBD-7 versus a heat-killed strain could exert an enhanced cell-mediated immune (CMI) response, as well as a humoral immune response capable of neutralizing the RBD and ACE2 interaction. In a two-dose vaccination model, rMpg-RBD-7 in a two-dose vaccination could also exert a stronger CMI and humoral immune response to neutralize SARS-CoV-2 infections in pseudoviral or live virus infection systems, compared to single dose vaccinations of rMpg-RBD or two-dose RBD protein immunization. In conclusion, our data showed that rMpg-RBD-7 can lead to an enhanced CMI response and humoral immune responses in mice vaccinated with both single- or two-dose vaccination, highlighting its feasibility as a novel vaccine candidate for SARS-CoV-2. To the best of our knowledge, this study is the first in which mycobacteria is used as a delivery system for a SARS-CoV-2 vaccine.

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Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates

10.1101/2020.05.28.121640 ◽

2020 ◽

Cited By ~ 5

Author(s):

Jesse H. Erasmus ◽

Amit P. Khandhar ◽

Alexandra C. Walls ◽

Emily A. Hemann ◽

Megan A. O’Connor ◽

...

Keyword(s):

Single Dose ◽

Neutralizing Antibodies ◽

Global Economy ◽

Nonhuman Primates ◽

Vaccine Candidate ◽

Scale Up ◽

Igg Antibody ◽

Antibody Isotypes ◽

Rna Replicon

AbstractThe ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.

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Immunogenicity Studies of Bivalent Inactivated Virions of EV71/CVA16 Formulated with Submicron Emulsion Systems

BioMed Research International ◽

10.1155/2014/670506 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Chih-Wei Lin ◽

Chia-Chyi Liu ◽

Tsung-Chun Lu ◽

Shih-Jen Liu ◽

Yen-Hung Chow ◽

...

Keyword(s):

Single Dose ◽

Vaccine Candidate ◽

Emerging Infectious Diseases ◽

Foot And Mouth Disease ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Submicron Particles ◽

Emulsion Systems ◽

Submicron Emulsion ◽

Immunogenicity Study

We assessed two strategies for preparing candidate vaccines against hand, foot, and mouth disease (HFMD) caused mainly by infections of enterovirus (EV) 71 and coxsackievirus (CV) A16. We firstly design and optimize the potency of adjuvant combinations of emulsion-based delivery systems, using EV71 candidate vaccine as a model. We then perform immunogenicity studies in mice of EV71/CVA16 antigen combinations formulated with PELC/CpG. A single dose of inactivated EV71 virion (0.2 μg) emulsified in submicron particles was found (i) to induce potent antigen-specific neutralizing antibody responses and (ii) consistently to elicit broad antibody responses against EV71 neutralization epitopes. A single dose immunogenicity study of bivalent activated EV71/CVA16 virion formulated with either Alum or PELC/CpG adjuvant showed that CVA16 antigen failed to elicit CVA16 neutralizing antibody responses and did not affect EV71-specific neutralizing antibody responses. A boosting dose of emulsified EV71/CVA16 bivalent vaccine candidate was found to be necessary to achieve high seroconversion of CVA16-specific neutralizing antibody responses. The current results are important for the design and development of prophylactic vaccines against HFMD and other emerging infectious diseases.

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One dose of COVID-19 nanoparticle vaccine REVC-128 provides protection against SARS-CoV-2 challenge at two weeks post immunization

10.1101/2021.04.02.438218 ◽

2021 ◽

Author(s):

Maggie Gu ◽

Jonathan L. Torres ◽

Jack Greenhouse ◽

Shannon Wallace ◽

Chi-I Chiang ◽

...

Keyword(s):

Single Dose ◽

Tissue Damage ◽

Vaccine Candidate ◽

In Vivo Model ◽

Single Shot ◽

Virus Challenge ◽

Post Immunization ◽

Viral Loads ◽

Viral Spread

AbstractA COVID-19 vaccine with capability to induce early protection is needed to efficiently eliminate viral spread. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomain subunits with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titer at two weeks post immunization, which is significantly higher than titer induced by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for SARS-CoV-2 virus challenge was implemented at two weeks post a single dose of REVC-128 immunization. The results show that vaccination protects hamsters against SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage (lung and nares) for protected animals, compared with ~10% weight loss, higher viral loads and tissue damage in unprotected animals. Furthermore, the data show that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with a long history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine candidate to induce the earliest protection against SARS-CoV-2 infection.

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Enemy of My Enemy: A Novel Insect-Specific Flavivirus Offers a Promising Platform for a Zika Virus Vaccine

Vaccines ◽

10.3390/vaccines9101142 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1142

Author(s):

Danielle Porier ◽

Sarah Wilson ◽

Dawn Auguste ◽

Andrew Leber ◽

Sheryl Coutermarsh-Ott ◽

...

Keyword(s):

Public Health ◽

Single Dose ◽

Zika Virus ◽

Vaccine Development ◽

Vaccine Candidate ◽

Neutralizing Antibody ◽

Viral Disease ◽

Trade Offs

Vaccination remains critical for viral disease outbreak prevention and control, but conventional vaccine development typically involves trade-offs between safety and immunogenicity. We used a recently discovered insect-specific flavivirus as a vector in order to develop an exceptionally safe, flavivirus vaccine candidate with single-dose efficacy. To evaluate the safety and efficacy of this platform, we created a chimeric Zika virus (ZIKV) vaccine candidate, designated Aripo/Zika virus (ARPV/ZIKV). ZIKV has caused immense economic and public health impacts throughout the Americas and remains a significant public health threat. ARPV/ZIKV vaccination showed exceptional safety due to ARPV/ZIKV’s inherent vertebrate host-restriction. ARPV/ZIKV showed no evidence of replication or translation in vitro and showed no hematological, histological or pathogenic effects in vivo. A single-dose immunization with ARPV/ZIKV induced rapid and robust neutralizing antibody and cellular responses, which offered complete protection against ZIKV-induced morbidity, mortality and in utero transmission in immune-competent and -compromised murine models. Splenocytes derived from vaccinated mice demonstrated significant CD4+ and CD8+ responses and significant cytokine production post-antigen exposure. Altogether, our results further support that chimeric insect-specific flaviviruses are a promising strategy to restrict flavivirus emergence via vaccine development.

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Protection Provided by an Encapsulated Live Attenuated ΔabcBAStrain of Brucella ovis against Experimental Challenge in a Murine Model

Clinical and Vaccine Immunology ◽

10.1128/cvi.00191-15 ◽

2015 ◽

Vol 22 (7) ◽

pp. 789-797 ◽

Cited By ~ 9

Author(s):

Ana Patrícia C. Silva ◽

Auricélio A. Macêdo ◽

Teane M. A. Silva ◽

Luana C. A. Ximenes ◽

Humberto M. Brandão ◽

...

Keyword(s):

Single Dose ◽

Murine Model ◽

Vaccine Candidate ◽

Wild Type ◽

Content Type ◽

Brucella Ovis ◽

Experimental Challenge

ABSTRACTThis study aimed to evaluate theBrucella ovisΔabcBAstrain as a vaccine candidate in the murine model. BALB/c mice were subcutaneously or intraperitoneally immunized with a single dose or three doses of theB. ovisΔabcBAstrain and then were challenged with wild-typeB. ovis. Single or multiple immunizations provided only mild protection, with significantly smaller numbers of wild-typeB. ovisCFU in the livers of immunized mice but not in the spleens. Encapsulation ofB. ovisΔabcBAsignificantly improved protection against experimental challenges in both BALB/c and C57BL/6 mice. Furthermore, immunization with encapsulatedB. ovisΔabcBAmarkedly prevented lesions in the spleens and livers of experimentally challenged mice. These results demonstrated that the encapsulatedB. ovisΔabcBAstrain confers protection to mice; therefore, this strain has potential as a vaccine candidate for rams.

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Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19

10.1101/2020.06.20.159715 ◽

2020 ◽

Author(s):

Simon P. Graham ◽

Rebecca K. McLean ◽

Alexandra J. Spencer ◽

Sandra Belij-Rammerstorfer ◽

Daniel Wright ◽

...

Keyword(s):

T Cells ◽

Single Dose ◽

Specific Antibody ◽

Adenoviral Vector ◽

Vaccine Candidate ◽

Clinical Development ◽

Antibody Responses ◽

S Protein ◽

Booster Immunisation ◽

Human Primate

AbstractClinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres.

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A single dose, BCG-adjuvanted SARS-CoV-2 vaccine induces Th1-polarized immunity and high-titre neutralizing antibodies in mice

10.1101/2020.12.10.419044 ◽

2020 ◽

Author(s):

Claudio Counoupas ◽

Alberto O. Stella ◽

Nayan D. Bhattacharyya ◽

Alice Grey ◽

Karishma Patel ◽

...

Keyword(s):

Single Dose ◽

Neutralizing Antibodies ◽

Protective Immunity ◽

Vaccine Candidate ◽

Rapid Development ◽

Population Level ◽

High Titre ◽

Spike Protein ◽

Cold Chain ◽

Igg Antibody

AbstractNext-generation vaccines that are safe, effective and with equitable access globally are required to prevent SARS-CoV-2 transmission at a population level. One strategy that has gained significant interest is to ‘repurpose’ existing licensed vaccines for use against COVID-19. In this report, we have exploited the immunostimulatory properties of bacille Calmette-Guérin (BCG), the vaccine for tuberculosis, to develop a SARS-CoV-2-specific and highly immunogenic vaccine candidate. Combination of BCG with a stabilized, trimeric form of the SARS-CoV-2 spike antigen promoted rapid development of virus-specific IgG antibodies in the sera of vaccinated mice, which could be further augmented by the addition of alum. This vaccine formulation, termed BCG:CoVac, induced a Th1-biased response both in terms of IgG antibody subclass and cytokine release by vaccine-specific CD4+ and CD8+ T cells. A single dose of BCG:CoVac was sufficient to induce high-titre SARS-CoV-2 neutralizing antibodies (NAbs) that were detectable as early as 2 weeks post-vaccination; NAb levels were greater than that seen in the sera of SARS-CoV-2-infected individuals. Boosting of BCG:CoVac-primed mice with a heterologous vaccine combination (spike protein plus alum) could further increase SARS-CoV-2 spike protein-specific antibody response. BCG:CoVac would be broadly applicable for all populations susceptible to SARS-CoV-2 infection and in particular could be readily incorporated into current vaccine schedules in countries where BCG is currently used.ImportanceEffective distribution of vaccine to low- and middle-income countries is critical for the control of the COVID-19 pandemic. To achieve this, vaccines must offer effective protective immunity yet should be cheap to manufacture and meet cold chain management requirements. This study describes a unique COVID-19 vaccine candidate, termed BCG:CoVac, that when delivered as a single dose induces potent SARS-CoV-2 specific immunity in mice, particularly through generation of high-titre, anti-viral neutralising antibodies. BCG:CoVac is built on safe and well-characterised vaccine components: 1) the BCG vaccine, used for control of tuberculosis since 1921 which also has remarkable ‘off target’ effects, protecting children and the elderly against diverse respiratory viral infections; 2) Alhydrogel adjuvant (Alum), a low cost, globally accessible vaccine adjuvant with an excellent safety record in humans (part of >20 licensed human vaccines and in use >70 years); 3) Stabilized, trimeric SARS-CoV-2 spike protein, which stimulates immune specificity for COVID-19. Further assessment in humans will determine if BCG:CoVac can impart protective immunity against not only SARS-CoV-2, but also other respiratory infections where BCG has known efficacy.

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An enveloped virus-like particle vaccine expressing a stabilized prefusion form of the SARS-CoV-2 spike protein elicits potent immunity after a single dose

10.1101/2021.04.28.441832 ◽

2021 ◽

Author(s):

Anne-Catherine Fluckiger ◽

Barthelemy Ontsouka ◽

Jasminka Bozic ◽

Abebaw Diress ◽

Tanvir Ahmed ◽

...

Keyword(s):

Single Dose ◽

Vaccine Candidate ◽

Aluminum Phosphate ◽

Antibody Binding ◽

Spike Protein ◽

List Type ◽

Enveloped Virus ◽

Virus Like Particle ◽

Syrian Golden Hamsters ◽

Dose Vaccine

AbstractDevelopment of efficacious single dose vaccines would substantially aid efforts to stop the uncontrolled spread of the COVID-19 pandemic. We evaluated enveloped virus-like particles (eVLPs) expressing various forms of the SARS-CoV-2 spike protein and several adjuvants in an effort to identify a COVID-19 vaccine candidate efficacious after a single dose. The eVLPs expressing a modified prefusion form of SARS-CoV-2 spike protein were selected as they induced the highest antibody binding titers and neutralizing activity after a single injection in mice. Formulation of SARS-CoV-2 S eVLPs with aluminum phosphate resulted in balanced induction of IgG2 and IgG1 isotypes and antibody binding and neutralization titers were undiminished for more than 3 months after a single immunization. A single dose of this candidate, VBI-2902a (prefusion S eVLPs formulated with aluminum phosphate), protected Syrian golden hamsters from challenge with SARS-CoV-2 and supports the on-going clinical evaluation of VBI-2902a as a potential single dose vaccine against COVID-19.HighlightsVBI-2902a is a VLP-based vaccine candidate against SARS-COV-2VBI-2902a contains VLPs pseudotyped with a modified prefusion SARS-COV-2 S in Alum.VBI-2902a induces robust neutralization antibody response against SARS-COV-2 SVBI-2902a protects hamsters from SARS-CoV-2 induced lung inflammationA single dose of VBI-2902a provides protective benefit in hamsters

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Immunogenicity and protective efficacy of one- and two-dose regimens of the Ad26.COV2.S COVID-19 vaccine candidate in adult and aged rhesus macaques

10.1101/2020.11.17.368258 ◽

2020 ◽

Author(s):

Laura Solforosi ◽

Harmjan Kuipers ◽

Sietske K. Rosendahl Huber ◽

Joan E.M. van der Lubbe ◽

Liesbeth Dekking ◽

...

Keyword(s):

Single Dose ◽

Vaccine Candidate ◽

Protective Efficacy ◽

Rhesus Macaques ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Upper Respiratory Tract ◽

Post Dose ◽

Early Indication

AbstractSafe and effective coronavirus disease (COVID)-19 vaccines are urgently needed to control the ongoing pandemic. While single-dose vaccine regimens would provide multiple advantages, two doses may improve the magnitude and durability of immunity and protective efficacy. We assessed one- and two-dose regimens of the Ad26.COV2.S vaccine candidate in adult and aged non-human primates (NHP). A two-dose Ad26.COV2.S regimen induced higher peak binding and neutralizing antibody responses compared to a single dose. In one-dose regimens neutralizing antibody responses were stable for at least 14 weeks, providing an early indication of durability. Ad26.COV2.S induced humoral immunity and Th1 skewed cellular responses in aged NHP that were comparable to adult animals. Importantly, aged Ad26.COV2.S-vaccinated animals challenged 3 months post -dose 1 with a SARS-CoV-2 spike G614 variant showed near complete lower and substantial upper respiratory tract protection for both regimens. These are the first NHP data showing COVID-19 vaccine protection against the SARS-CoV-2 spike G614 variant and support ongoing clinical Ad26.COV2.S development.SummaryCOVID-19 vaccines are urgently needed and while single-dose vaccines are preferred, two-dose regimens may improve efficacy. We show improved Ad26.COV2.S immunogenicity in non-human primates after a second vaccine dose, while both regimens protected aged animals against SARS-CoV-2 disease.

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