adjuvanted vaccine
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2021 ◽  
Vol 12 ◽  
Author(s):  
Fan Zhou ◽  
Lena Hansen ◽  
Gabriel Pedersen ◽  
Gunnveig Grødeland ◽  
Rebecca Cox

The highly pathogenic avian influenza H5N1 viruses constantly evolve and give rise to novel variants that have caused widespread zoonotic outbreaks and sporadic human infections. Therefore, vaccines capable of eliciting broadly protective antibody responses are desired and under development. We here investigated the magnitude, kinetics and protective efficacy of the multi-faceted humoral immunity induced by vaccination in healthy adult volunteers with a Matrix M adjuvanted virosomal H5N1 vaccine. Vaccinees were given escalating doses of adjuvanted vaccine (1.5μg, 7.5μg, or 30μg), or a non-adjuvanted vaccine (30μg). An evaluation of sera from vaccinees against pseudotyped viruses covering all (sub)clades isolated from human H5N1 infections demonstrated that the adjuvanted vaccines (7.5μg and 30μg) could elicit rapid and robust increases of broadly cross-neutralizing antibodies against all clades. In addition, the adjuvanted vaccines also induced multifaceted antibody responses including hemagglutinin stalk domain specific, neuraminidase inhibiting, and antibody-dependent cellular cytotoxicity inducing antibodies. The lower adjuvanted dose (1.5µg) showed delayed kinetics, whilst the non-adjuvanted vaccine induced overall lower levels of antibody responses. Importantly, we demonstrate that human sera post vaccination with the adjuvanted (30μg) vaccine provided full protection against a lethal homologous virus challenge in mice. Of note, when combining our data from mice and humans we identified the neutralizing and neuraminidase inhibiting antibody titers as correlates of in vivo protection.


npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mayuresh M. Abhyankar ◽  
Barbara J. Mann ◽  
Jeffrey M. Sturek ◽  
Savannah Brovero ◽  
G. Brett Moreau ◽  
...  

AbstractWe developed a SARS-CoV-2 spike subunit vaccine formulation containing dual TLR ligand liposome adjuvant. The vaccine-induced robust systemic neutralizing antibodies and completely protected mice from a lethal challenge. Two immunizations protected against lung injury and cleared the virus from lungs upon challenge. The adjuvanted vaccine also elicited systemic and local anti-Spike IgA which can be an important feature for a COVID-19 vaccine.


Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1347
Author(s):  
Joshua M. Royal ◽  
Carrie A. Simpson ◽  
Alison A. McCormick ◽  
Amanda Phillips ◽  
Steve Hume ◽  
...  

Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain (CoV-RBD121) and conjugated to a modified tobacco mosaic virus (TMV) nanoparticle. In vitro, CoV-RBD121 bound to the host virus receptor ACE2 and to the monoclonal antibody CR3022, a neutralizing antibody that blocks S binding to ACE2. The CoV-RBD121-NP vaccine candidate retained key SARS-CoV-2 spike protein epitopes, had consistent manufacturing release properties of safety, identity, and strength, and displayed stable potency when stored for 12 months at 2–8 °C or 22–28 °C. Immunogenicity studies revealed strong antibody responses in C57BL/6 mice with non-adjuvanted or adjuvanted (7909 CpG) formulations. The non-adjuvanted vaccine induced a balanced Th1/Th2 response and antibodies that recognized both the S1 domain and full S protein from SARS2-CoV-2, whereas the adjuvanted vaccine induced a Th1-biased response. Both adjuvanted and non-adjuvanted vaccines induced virus neutralizing titers as measured by three different assays. Collectively, these data showed the production of a stable candidate vaccine for COVID-19 through the association of the SARS-CoV-2 RBD with the TMV-like nanoparticle.


Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 996
Author(s):  
Ntungufhadzeni M. Rathogwa ◽  
Katherine A. Scott ◽  
Pamela Opperman ◽  
Jacques Theron ◽  
Francois F. Maree

The effective control of foot-and-mouth disease (FMD) relies strongly on the separation of susceptible and infected livestock or susceptible livestock and persistently infected wildlife, vaccination, and veterinary sanitary measures. Vaccines affording protection against multiple serotypes for longer than six months and that are less reliant on the cold chain during handling are urgently needed for the effective control of FMD in endemic regions. Although much effort has been devoted to improving the immune responses elicited through the use of modern adjuvants, their efficacy is dependent on the formulation recipe, target species and administration route. Here we compared and evaluated the efficacy of two adjuvant formulations in combination with a structurally stabilized SAT2 vaccine antigen, designed to have improved thermostability, antigen shelf-life and longevity of antibody response. Protection mediated by the Montanide ISA 206B-adjuvanted or Quil-A Saponin-adjuvanted SAT2 vaccines were comparable. The Montanide ISA 206B-adjuvanted vaccine elicited a higher SAT2 neutralizing antibody response and three times higher levels of systemic IFN-γ responses at 14- and 28-days post-vaccination (dpv) were observed compared to the Quil-A Saponin-adjuvanted vaccine group. Interestingly, serum antibodies from the immunized animals reacted similarly to the parental vaccine virus and viruses containing mutations in the VP2 protein that simulate antigenic drift in nature.


2021 ◽  
Vol 6 (61) ◽  
pp. eabh3634
Author(s):  
Maria Pino ◽  
Talha Abid ◽  
Susan Pereira Ribeiro ◽  
Venkata Viswanadh Edara ◽  
Katharine Floyd ◽  
...  

Ongoing SARS-CoV-2 vaccine development is focused on identifying stable, cost-effective, and accessible candidates for global use, specifically in low and middle-income countries. Here, we report the efficacy of a rapidly scalable, novel yeast expressed SARS-CoV-2 specific receptor-binding domain (RBD) based vaccine in rhesus macaques. We formulated the RBD immunogen in alum, a licensed and an emerging alum adsorbed TLR-7/8 targeted, 3M-052-alum adjuvants. The RBD+3M-052-alum adjuvanted vaccine promoted better RBD binding and effector antibodies, higher CoV-2 neutralizing antibodies, improved Th1 biased CD4+T cell reactions, and increased CD8+ T cell responses when compared to the alum-alone adjuvanted vaccine. RBD+3M-052-alum induced a significant reduction of SARS-CoV-2 virus in respiratory tract upon challenge, accompanied by reduced lung inflammation when compared with unvaccinated controls. Anti-RBD antibody responses in vaccinated animals inversely correlated with viral load in nasal secretions and BAL. RBD+3M-052-alum blocked a post SARS-CoV-2 challenge increase in CD14+CD16++ intermediate blood monocytes, and Fractalkine, MCP-1, and TRAIL in the plasma. Decreased plasma analytes and intermediate monocyte frequencies correlated with reduced nasal and BAL viral loads. Lastly, RBD-specific plasma cells accumulated in the draining lymph nodes and not in the bone marrow, contrary to previous findings. Together, these data show that a yeast expressed, RBD-based vaccine+3M-052-alum provides robust immune responses and protection against SARS-CoV-2, making it a strong and scalable vaccine candidate.


Vaccine ◽  
2021 ◽  
Author(s):  
Esther Redondo ◽  
Georgina Drago ◽  
Juan Luis López-Belmonte ◽  
Jose María Guillén ◽  
Helene Bricout ◽  
...  

Author(s):  
Ainara Mira-Iglesias ◽  
F. Xavier López-Labrador ◽  
Javier García-Rubio ◽  
Beatriz Mengual-Chuliá ◽  
Miguel Tortajada-Girbés ◽  
...  

Influenza vaccination is annually recommended for specific populations at risk, such as older adults. We estimated the 2018/2019 influenza vaccine effectiveness (IVE) overall, by influenza subtype, type of vaccine, and by time elapsed since vaccination among subjects 65 years old or over in a multicenter prospective study in the Valencia Hospital Surveillance Network for the Study of Influenza and other Respiratory Viruses (VAHNSI, Spain). Information about potential confounders was obtained from clinical registries and/or by interviewing patients and vaccination details were only ascertained by registries. A test-negative design was performed in order to estimate IVE. As a result, IVE was estimated at 46% (95% confidence interval (CI): (16%, 66%)), 41% (95% CI: (−34%, 74%)), and 45% (95% CI: (7%, 67%)) against overall influenza, A(H1N1)pdm09 and A(H3N2), respectively. An intra-seasonal not relevant waning effect was detected. The IVE for the adjuvanted vaccine in ≥75 years old was 45% (2%, 69%) and for the non-adjuvanted vaccine in 65–74 years old was 59% (−16%, 86%). Thus, our data revealed moderate vaccine effectiveness against influenza A(H3N2) and not significant against A(H1N1)pdm09. Significant protection was conferred by the adjuvanted vaccine to patients ≥75 years old. Moreover, an intra-seasonal not relevant waning effect was detected, and a not significant IVE decreasing trend was observed over time.


Author(s):  
Keith Joseph Chappell ◽  
Francesca L. Mordant ◽  
Zheyi Li ◽  
Danushka K. Wijesundara ◽  
Paula Ellenberg ◽  
...  

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