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2021 ◽  
Daniel A.M. Villela ◽  
Tatiana Guimarães de Noronha ◽  
Leonardo S Bastos ◽  
Antonio G. F. Pacheco ◽  
Oswaldo G. Cruz ◽  

Background. Mass vaccination campaigns started in Brazil on January/2021 with CoronaVac followed by ChAdOx1 nCov-19, and BNT162b2 mRNA vaccines. Target populations initially included vulnerable groups such as people older than 80 years, with comorbidities, of indigenous origin, and healthcare workers. Younger age groups were gradually included. Methods. A national cohort of 66.3 million records was compiled by linking registry-certified COVID-19 vaccination records from the Brazilian National Immunization Program with information on severe COVID-19 cases and deaths. Cases and deaths were aggregated by state and age group. Mixed-effects Poisson models were used to estimate the rate of severe cases and deaths among vaccinated and unvaccinated individuals, and the corresponding estimates of vaccine effectiveness by vaccine platform and age group. The study period is from mid-January to mid-July 2021. Results. Estimates of vaccine effectiveness preventing deaths were highest at 97.9% (95% CrI: 93.5-99.8) among 20-39 years old with ChAdOx1 nCov-19, at 82.7% (95% CrI: 80.7-84.6) among 40-59 years old with CoronaVac, and at 89.9% (87.8--91.8) among 40-59 years old with partial immunization of BNT162b2. For all vaccines combined in the full regimen, the effectiveness preventing severe cases among individuals aged 80+ years old was 35.9% (95% CrI: 34.9-36.9) which is lower than that observed for individuals aged 60-79 years (61.0%, 95% CrI: 60.5-61.5). Conclusion. Despite varying effectiveness estimates, Brazil′s population benefited from vaccination in preventing severe COVID-19 outcomes. Results, however, suggest significant vaccine-specific reductions in effectiveness by age, given by differences between age groups 60-79 years and over 80 years.

2021 ◽  
Christopher Chevillard ◽  
Axelle Amen ◽  
Solene Besson ◽  
Dalil Hannani ◽  
Isabelle Bally ◽  

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown that vaccine preparedness is critical to anticipate a fast response to emergent pathogens with high infectivity. To rapidly reach herd immunity, an affordable, easy to store and versatile vaccine platform is thus desirable. We previously designed a non-infectious adenovirus-inspired nanoparticle (ADDomer), and in the present work, we efficiently decorated this original vaccine platform with glycosylated receptor binding domain (RBD) of SARS-CoV-2. Cryo-Electron Microscopy structure revealed that up to 60 copies of this antigenic domain were bound on a single ADDomer particle with the symmetrical arrangements of a dodecahedron. Mouse immunization with the RBD decorated particles showed as early as the first immunization a significant anti-coronavirus humoral response, which was boosted after a second immunization. Neutralization assays with spike pseudo-typed-virus demonstrated the elicitation of strong neutralization titers. Remarkably, the existence of pre-existing immunity against adenoviral-derived particles enhanced the humoral response against SARS-CoV-2. This plug and play vaccine platform revisits the way of using adenovirus to combat emergent pathogens while potentially taking advantage of the adenovirus pre-immunity.

2021 ◽  
Dominik A. Rothen ◽  
Pascal S. Krenger ◽  
Aleksandra Nonic ◽  
Ina Balke ◽  
Anne-Cathrine S. Vogt ◽  

AbstractBackgroundThe highly contagious SARS-CoV-2 is mainly transmitted by respiratory droplets and aerosols. Consequently, people are required to wear masks and maintain a social distance to avoid spreading of the virus. Despite the success of the commercially available vaccines, the virus is still uncontained globally. Given the tropism of SARS-CoV-2, a mucosal immune reaction would help to reduce viral shedding and transmission locally. Only seven out of hundreds of ongoing clinical trials are testing the intranasal delivery of COVID-19 vaccines.MethodsIn the current study, we tested in murine model the immunogenicity of a conventional vaccine platform based on virus-like particles (VLPs) displaying RBD of SARS-CoV-2 for intranasal vaccination. The candidate vaccine, CuMVTT-RBD, has been immunologically optimized to incorporate tetanus-toxin and is self-adjuvanted with TLR7/8 ligands.ResultsCuMVTT-RBD elicited strong RBD- and spike- specific systemic IgG and IgA antibody responses of high avidity. Local immune responses were assessed and results demonstrate strong mucosal antibody and plasma cell production in lung tissue. The induced systemic antibodies could efficiently recognize and neutralize different Variants of Concerns of mutated SARS-CoV-2 RBDs.ConclusionIn summary, intranasal vaccination with CuMVTT-RBD shows high immunogenicity and induces protective systemic and local specific antibody response against SARS-CoV-2 and its variants.One sentence summaryEvaluation of an intransal administrated conventional VLP-based vaccine against COVID-19 in a murine model.

2021 ◽  
Vol 8 ◽  
José M. Rojas ◽  
Noemí Sevilla ◽  
Verónica Martín

Peste des petits ruminants virus (PPRV) is a virus that mainly infects goats and sheep causing significant economic loss in Africa and Asia, but also posing a serious threat to Europe, as recent outbreaks in Georgia (2016) and Bulgaria (2018) have been reported. In order to carry out the eradication of PPRV, an objective set for 2030 by the Office International des Epizooties (OIE) and the Food and Agriculture Organization of the United Nations (FAO), close collaboration between governments, pharmaceutical companies, farmers and researchers, among others, is needed. Today, more than ever, as seen in the response to the SARS-CoV2 pandemic that we are currently experiencing, these goals are feasible. We summarize in this review the current vaccination approaches against PPRV in the field, discussing their advantages and shortfalls, as well as the development and generation of new vaccination strategies, focusing on the potential use of adenovirus as vaccine platform against PPRV and more broadly against other ruminant pathogens.

2021 ◽  
Vol 11 (1) ◽  
Toshifumi Imagawa ◽  
Masahiko Ito ◽  
Mami Matsuda ◽  
Kenji Nakashima ◽  
Yuhei Tokunaga ◽  

AbstractThe global incidence of dengue, which is caused by dengue virus (DENV) infection, has grown dramatically in recent decades and secondary infection with heterologous serotype of the virus may cause severe symptoms. Efficacious dengue vaccines should be able to provide long-lasting immunity against all four DENV serotypes simultaneously. In this study, we constructed a novel vaccine platform based on tetravalent dengue virus-like particles (DENV-LPs) in which envelope (E) protein carried a FLAG tag sequence at the position located not only in the exterior loop on the protruding domain but outside of dimerization interface of the protein. We demonstrated an effective strategy to produce the DENV-LPs by transient transfection with expression plasmids for pre-membrane and E proteins of DENV-1 to DENV-4 in mammalian cells and to concentrate and purify them with one-step affinity chromatography. Characteristic features of VLPs such as particle size, shape and density were comparable to flavivirus-like particles reported. The neutralizing activity against all four DENV serotypes was successfully induced by immunization with the purified tetravalent VLPs in mice. Simple, one-step purification systems for VLP vaccine platforms using epitope-tagging strategy should be advantageous for vaccine development not only for dengue but for emerging pandemics in the future.

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 957
Soo-Kyung Jeong ◽  
Yoon-Ki Heo ◽  
Jei-Hyun Jeong ◽  
Su-Jin Ham ◽  
Jung-Sun Yum ◽  

The development of COVID-19 vaccines is critical in controlling global health issues under the COVID-19 pandemic. The subunit vaccines are the safest and most widely used vaccine platform and highly effective against a multitude of infectious diseases. An adjuvant is essential for subunit vaccines to enhance the magnitude and durability of immune responses. In this study, we determined whether a combination of toll-like receptor (TLR)1/2 and TLR3 agonists (L-pampo) can be a potent adjuvant for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine. We measured a neutralizing antibody (nAb) and an angiotensin-converting enzyme 2 (ACE2) receptor-blocking antibody against SARS-CoV-2 receptor-binding domain (RBD). We also detected interferon-gamma (IFN-γ) production by using ELISPOT and ELISA assays. By employing a ferret model, we detected nAbs and IFN-γ producing cells and measured viral load in nasal wash after the challenge of SARS-CoV-2. We found that SARS-CoV-2 antigens with L-pampo stimulated robust humoral and cellular immune responses. The efficacy of L-pampo was higher than the other adjuvants. Furthermore, in the ferret model, SARS-CoV-2 antigens with L-pampo elicited nAb response and antigen-specific cellular immune response against SARS-CoV-2, resulting in substantially decreased viral load in their nasal wash. Our study suggests that SARS-CoV-2 antigens formulated with TLR agonists, L-pampo, can be a potent subunit vaccine to promote sufficient protective immunity against SARS-CoV-2.

2021 ◽  
Vol 6 (4) ◽  

Vaccine such as influenza vaccine, is administered in stable transplant recipients, although live attenuated virus vaccines are contraindicated, generally due to risk of disseminated infection [1, 2]. Neither efficacy, safety, nor durability are well known in transplant recipients due to exclusion of them from recent COVID-19 vaccine trials [1, 2]. Currently, there are no SARS-CoV-2 vaccine platforms using attenuated live virus approved in phase III trials. Nevertheless, if they are approved for use, concerns, including potential decrease in efficacy in immunocompromised patients, potential for vaccine-related allograft rejection, unknown durability of the immune response, and long-term safety data still exist. Due to experience with neither the influenza vaccine nor the adjuvant recombinant zoster vaccine having been related to allograft rejection, successful administration of influenza and adjuvanted recombinant zoster vaccines to stable transplant recipients, and unanticipated vaccine-related adverse events to the allograft having not borne out, the influenza and adjuvanted recombinant zoster vaccines are able to be extrapolated to COVID-19 vaccines [2, 3]. In immunocompromised host, concerns for adenoviral vector vaccines are focused on a viral infection, but these concerns have no scientific evidence. Although newly approved adenoviral-vector use for vaccination, this vaccine platform has been used for decades for gene therapy for cancer and other rare diseases. Inactivated virus and protein subunit vaccine platforms that have been used in transplant recipients for other infections, such as human papilloma virus, pertussis, and hepatitis A and B, are currently under investigation for SARS-CoV-2 (COVID-19) infection in transplant recipients [2].

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Mona O. Mohsen ◽  
Dominik Rothen ◽  
Ina Balke ◽  
Byron Martina ◽  
Vilija Zeltina ◽  

AbstractMERS-CoV continues to cause human outbreaks, so far in 27 countries worldwide following the first registered epidemic in Saudi Arabia in 2012. In this study, we produced a nanovaccine based on virus-like particles (VLPs). VLPs are safe vaccine platforms as they lack any replication-competent genetic material, and are used since many years against hepatitis B virus (HBV), hepatitis E virus (HEV) and human papilloma virus (HPV). In order to produce a vaccine that is readily scalable, we genetically fused the receptor-binding motif (RBM) of MERS-CoV spike protein into the surface of cucumber-mosaic virus VLPs. The employed CuMVTT-VLPs represent a new immunologically optimized vaccine platform incorporating a universal T cell epitope derived from tetanus toxin (TT). The resultant vaccine candidate (mCuMVTT-MERS) is a mosaic particle and consists of unmodified wild type monomers and genetically modified monomers displaying RBM, co-assembling within E. coli upon expression. mCuMVTT-MERS vaccine is self-adjuvanted with ssRNA, a TLR7/8 ligand which is spontaneously packaged during the bacterial expression process. The developed vaccine candidate induced high anti-RBD and anti-spike antibodies in a murine model, showing high binding avidity and an ability to completely neutralize MERS-CoV/EMC/2012 isolate, demonstrating the protective potential of the vaccine candidate for dromedaries and humans.

2021 ◽  
David P Maison ◽  
Lauren L Ching ◽  
Sean B Cleveland ◽  
Alanna C Tseng ◽  
Eileen Nakano ◽  

SARS-CoV-2 worldwide emergence and evolution has resulted in variants containing mutations resulting in immune evasive epitopes that decrease vaccine efficacy. We acquired clinical samples, analyzed SARS-CoV-2 genomes, used the most worldwide emerged spike mutations from Variants of Concern/Interest, and developed an algorithm for monitoring the SARS-CoV-2 vaccine platform. The algorithm partitions logarithmic-transformed prevalence data monthly and Pearson's correlation determines exponential emergence. The SARS-CoV-2 genome evaluation indicated 49 mutations. Nine of the ten most worldwide prevalent (>70%) spike protein changes have r-values >0.9. The tenth, D614G, has a prevalence >99% and r-value of 0.67. The resulting algorithm is based on the patterns these ten substitutions elucidated. The strong positive correlation of the emerged spike protein changes and algorithmic predictive value can be harnessed in designing vaccines with relevant immunogenic epitopes. SARS-CoV-2 is predicted to remain endemic and continues to evolve, so must SARS-CoV-2 monitoring and next-generation vaccine design.

2021 ◽  
Vol 12 ◽  
Axel T. Lehrer ◽  
Eleanore Chuang ◽  
Madhuri Namekar ◽  
Caitlin A. Williams ◽  
Teri Ann S. Wong ◽  

Ebola (EBOV), Marburg (MARV) and Sudan (SUDV) viruses are the three filoviruses which have caused the most fatalities in humans. Transmission from animals into the human population typically causes outbreaks of limited scale in endemic regions. In contrast, the 2013-16 outbreak in several West African countries claimed more than 11,000 lives revealing the true epidemic potential of filoviruses. This is further emphasized by the difficulty seen with controlling the 2018-2020 outbreak of EBOV in the Democratic Republic of Congo (DRC), despite the availability of two emergency use-approved vaccines and several experimental therapeutics targeting EBOV. Moreover, there are currently no vaccine options to protect against the other epidemic filoviruses. Protection of a monovalent EBOV vaccine against other filoviruses has never been demonstrated in primate challenge studies substantiating a significant void in capability should a MARV or SUDV outbreak of similar magnitude occur. Herein we show progress on developing vaccines based on recombinant filovirus glycoproteins (GP) from EBOV, MARV and SUDV produced using the Drosophila S2 platform. The highly purified recombinant subunit vaccines formulated with CoVaccine HT™ adjuvant have not caused any safety concerns (no adverse reactions or clinical chemistry abnormalities) in preclinical testing. Candidate formulations elicit potent immune responses in mice, guinea pigs and non-human primates (NHPs) and consistently produce high antigen-specific IgG titers. Three doses of an EBOV candidate vaccine elicit full protection against lethal EBOV infection in the cynomolgus challenge model while one of four animals infected after only two doses showed delayed onset of Ebola Virus Disease (EVD) and eventually succumbed to infection while the other three animals survived challenge. The monovalent MARV or SUDV vaccine candidates completely protected cynomolgus macaques from infection with lethal doses of MARV or SUDV. It was further demonstrated that combinations of MARV or SUDV with the EBOV vaccine can be formulated yielding bivalent vaccines retaining full efficacy. The recombinant subunit vaccine platform should therefore allow the development of a safe and efficacious multivalent vaccine candidate for protection against Ebola, Marburg and Sudan Virus Disease.

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