Browsing by Subject "Viral Vaccines"

Now showing 1 - 7 of 7

Open Access
A genetically engineered, stem-cell-derived cellular vaccine.
(Cell reports. Medicine, 2022-12) Cooper, Amanda; Sidaway, Adam; Chandrashekar, Abishek; Latta, Elizabeth; Chakraborty, Krishnendu; Yu, Jingyou; McMahan, Katherine; Giffin, Victoria; Manickam, Cordelia; Kroll, Kyle; Mosher, Matthew; Reeves, R Keith; Gam, Rihab; Arthofer, Elisa; Choudhry, Modassir; Henley, Tom; Barouch, Dan H
Despite rapid clinical translation of COVID-19 vaccines in response to the global pandemic, an opportunity remains for vaccine technology innovation to address current limitations and meet challenges of inevitable future pandemics. We describe a universal vaccine cell (UVC) genetically engineered to mimic natural physiological immunity induced upon viral infection of host cells. Cells engineered to express the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike as a representative viral antigen induce robust neutralizing antibodies in immunized non-human primates. Similar titers generated in this established non-human primate (NHP) model have translated into protective human neutralizing antibody levels in SARS-CoV-2-vaccinated individuals. Animals vaccinated with ancestral spike antigens and subsequently challenged with SARS-CoV-2 Delta variant in a heterologous challenge have an approximately 3 log decrease in viral subgenomic RNA in the lungs. This cellular vaccine is designed as a scalable cell line with a modular poly-antigenic payload, allowing for rapid, large-scale clinical manufacturing and use in an evolving viral variant environment.
Open Access
Alphavirus Replicon Particle Vaccine Breaks B Cell Tolerance and Rapidly Induces IgG to Murine Hematolymphoid Tumor Associated Antigens.
(Frontiers in immunology, 2022-01) Su, Hsuan; Imai, Kazuhiro; Jia, Wei; Li, Zhiguo; DiCioccio, Rachel A; Serody, Jonathan S; Poe, Jonathan C; Chen, Benny J; Doan, Phuong L; Sarantopoulos, Stefanie
De novo immune responses to myeloid and other blood-borne tumors are notably limited and ineffective, making our ability to promote immune responses with vaccines a major challenge. While focus has been largely on cytotoxic cell-mediated tumor eradication, B-cells and the antibodies they produce also have roles in anti-tumor responses. Indeed, therapeutic antibody-mediated tumor cell killing is routinely employed in patients with hematolymphoid cancers, but whether endogenous antibody responses can be incited to blood-born tumors remains poorly studied. A major limitation of immunoglobulin therapies is that cell surface expression of tumor-associated antigen (TAA) targets is dynamic and varied, making promotion of polyclonal, endogenous B cell responses appealing. Since many TAAs are self-antigens, developing tumor vaccines that enable production of antibodies to non-polymorphic antigen targets remains a challenge. As B cell responses to RNA vaccines are known to occur, we employed the Viral Replicon Particles (VRP) which was constructed to encode mouse FLT3. The VRP-FLT3 vaccine provoked a rapid IgG B-cell response to this self-antigen in leukemia and lymphoma mouse models. In addition, IgGs to other TAAs were also produced. Our data suggest that vaccination with RNA viral particle vectors incites a loss of B-cell tolerance that enables production of anti-tumor antibodies. This proof of principle work provides impetus to employ such strategies that lead to a break in B-cell tolerance and enable production of broadly reactive anti-TAA antibodies as potential future therapeutic agents for patients with hematolymphoid cancers.
Open Access
Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine.
(Nature biomedical engineering, 2022-07-04) Wang, Zhenzhen; Popowski, Kristen D; Zhu, Dashuai; de Juan Abad, Blanca López; Wang, Xianyun; Liu, Mengrui; Lutz, Halle; De Naeyer, Nicole; DeMarco, C Todd; Denny, Thomas N; Dinh, Phuong-Uyen C; Li, Zhenhua; Cheng, Ke
The first two mRNA vaccines against infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that were approved by regulators require a cold chain and were designed to elicit systemic immunity via intramuscular injection. Here we report the design and preclinical testing of an inhalable virus-like-particle as a COVID-19 vaccine that, after lyophilisation, is stable at room temperature for over three months. The vaccine consists of a recombinant SARS-CoV-2 receptor-binding domain (RBD) conjugated to lung-derived exosomes which, with respect to liposomes, enhance the retention of the RBD in both the mucus-lined respiratory airway and in lung parenchyma. In mice, the vaccine elicited RBD-specific IgG antibodies, mucosal IgA responses and CD4⁺ and CD8⁺ T cells with a Th1-like cytokine expression profile in the animals' lungs, and cleared them of SARS-CoV-2 pseudovirus after a challenge. In hamsters, two doses of the vaccine attenuated severe pneumonia and reduced inflammatory infiltrates after a challenge with live SARS-CoV-2. Inhalable and room-temperature-stable virus-like particles may become promising vaccine candidates.
Open Access
Infectious virion capture by HIV-1 gp120-specific IgG from RV144 vaccinees.
(J Virol, 2013-07) Liu, Pinghuang; Yates, Nicole L; Shen, Xiaoying; Bonsignori, Mattia; Moody, M Anthony; Liao, Hua-Xin; Fong, Youyi; Alam, S Munir; Overman, R Glenn; Denny, Thomas; Ferrari, Guido; Ochsenbauer, Christina; Kappes, John C; Polonis, Victoria R; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Montefiori, David C; Gilbert, Peter; Michael, Nelson L; Kim, Jerome H; Haynes, Barton F; Tomaras, Georgia D
The detailed examination of the antibody repertoire from RV144 provides a unique template for understanding potentially protective antibody functions. Some potential immune correlates of protection were untested in the correlates analyses due to inherent assay limitations, as well as the need to keep the correlates analysis focused on a limited number of endpoints to achieve statistical power. In an RV144 pilot study, we determined that RV144 vaccination elicited antibodies that could bind infectious virions (including the vaccine strains HIV-1 CM244 and HIV-1 MN and an HIV-1 strain expressing transmitted/founder Env, B.WITO.c). Among vaccinees with the highest IgG binding antibody profile, the majority (78%) captured the infectious vaccine strain virus (CM244), while a smaller proportion of vaccinees (26%) captured HIV-1 transmitted/founder Env virus. We demonstrated that vaccine-elicited HIV-1 gp120 antibodies of multiple specificities (V3, V2, conformational C1, and gp120 conformational) mediated capture of infectious virions. Although capture of infectious HIV-1 correlated with other humoral immune responses, the extent of variation between these humoral responses and virion capture indicates that virion capture antibodies occupy unique immunological space.
Open Access
Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.
(Nature, 2021-06) Saunders, Kevin O; Lee, Esther; Parks, Robert; Martinez, David R; Li, Dapeng; Chen, Haiyan; Edwards, Robert J; Gobeil, Sophie; Barr, Maggie; Mansouri, Katayoun; Alam, S Munir; Sutherland, Laura L; Cai, Fangping; Sanzone, Aja M; Berry, Madison; Manne, Kartik; Bock, Kevin W; Minai, Mahnaz; Nagata, Bianca M; Kapingidza, Anyway B; Azoitei, Mihai; Tse, Longping V; Scobey, Trevor D; Spreng, Rachel L; Rountree, R Wes; DeMarco, C Todd; Denny, Thomas N; Woods, Christopher W; Petzold, Elizabeth W; Tang, Juanjie; Oguin, Thomas H; Sempowski, Gregory D; Gagne, Matthew; Douek, Daniel C; Tomai, Mark A; Fox, Christopher B; Seder, Robert; Wiehe, Kevin; Weissman, Drew; Pardi, Norbert; Golding, Hana; Khurana, Surender; Acharya, Priyamvada; Andersen, Hanne; Lewis, Mark G; Moore, Ian N; Montefiori, David C; Baric, Ralph S; Haynes, Barton F
Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)^1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID₅₀) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.
Open Access
Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques.
(Nature, 2020-10) Mercado, Noe B; Zahn, Roland; Wegmann, Frank; Loos, Carolin; Chandrashekar, Abishek; Yu, Jingyou; Liu, Jinyan; Peter, Lauren; McMahan, Katherine; Tostanoski, Lisa H; He, Xuan; Martinez, David R; Rutten, Lucy; Bos, Rinke; van Manen, Danielle; Vellinga, Jort; Custers, Jerome; Langedijk, Johannes P; Kwaks, Ted; Bakkers, Mark JG; Zuijdgeest, David; Rosendahl Huber, Sietske K; Atyeo, Caroline; Fischinger, Stephanie; Burke, John S; Feldman, Jared; Hauser, Blake M; Caradonna, Timothy M; Bondzie, Esther A; Dagotto, Gabriel; Gebre, Makda S; Hoffman, Emily; Jacob-Dolan, Catherine; Kirilova, Marinela; Li, Zhenfeng; Lin, Zijin; Mahrokhian, Shant H; Maxfield, Lori F; Nampanya, Felix; Nityanandam, Ramya; Nkolola, Joseph P; Patel, Shivani; Ventura, John D; Verrington, Kaylee; Wan, Huahua; Pessaint, Laurent; Van Ry, Alex; Blade, Kelvin; Strasbaugh, Amanda; Cabus, Mehtap; Brown, Renita; Cook, Anthony; Zouantchangadou, Serge; Teow, Elyse; Andersen, Hanne; Lewis, Mark G; Cai, Yongfei; Chen, Bing; Schmidt, Aaron G; Reeves, R Keith; Baric, Ralph S; Lauffenburger, Douglas A; Alter, Galit; Stoffels, Paul; Mammen, Mathai; Van Hoof, Johan; Schuitemaker, Hanneke; Barouch, Dan H
A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic^1-8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in non-human primates. Fifty-two rhesus macaques (Macaca mulatta) were immunized with Ad26 vectors that encoded S variants or sham control, and then challenged with SARS-CoV-2 by the intranasal and intratracheal routes^9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs after SARS-CoV-2 challenge. Titres of vaccine-elicited neutralizing antibodies correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in non-human primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials.
Open Access
Vaccines in 2017: Closing in on a Zika virus vaccine.
(Nature reviews. Immunology, 2018-02) Diamond, Michael S; Coyne, Carolyn B