scholarly journals Oral subunit SARS-CoV-2 vaccine induces systemic neutralizing IgG, IgA and cellular immune responses and can boost neutralizing antibody responses primed by an injected vaccine

2021 ◽  
Author(s):  
Jacob Pitcovski ◽  
Nady Gruzdev ◽  
Anna Abzach ◽  
Chen Katz ◽  
Ran Ben-Adiva ◽  
...  
Keyword(s):  
Immune Responses ◽  
Oral Vaccine ◽  
Protein A ◽  
Surface Protein ◽  
Neutralizing Antibody ◽  
Vaccination Schedule ◽  
Antigenic Drift ◽  
Post Dose ◽  
S Protein ◽  
N Protein

The rapid spread of the COVID-19 pandemic, with its devastating medical and economic impacts, triggered an unprecedented race toward development of effective vaccines. The commercialized vaccines are parenterally administered, which poses logistic challenges, while adequate protection at the mucosal sites of virus entry is questionable. Furthermore, essentially all vaccine candidates target the viral spike (S) protein, a surface protein that undergoes significant antigenic drift. This work aimed to develop an oral multi-antigen SARS-CoV-2 vaccine comprised of the receptor binding domain (RBD) of the viral S protein, two domains of the viral nucleocapsid protein (N), and heat-labile enterotoxin B (LTB), a potent mucosal adjuvant. The humoral, mucosal and cell-mediated immune responses of both a three-dose vaccination schedule and a heterologous subcutaneous prime and oral booster regimen were assessed in mice and rats, respectively. Mice receiving the oral vaccine compared to control mice showed significantly enhanced post-dose-3 virus-neutralizing antibody, anti-S IgG and IgA production and N-protein-stimulated IFN-γand IL-2 secretion by T cells. When administered as a booster to rats following parenteral priming with the viral S1 protein, the oral vaccine elicited markedly higher neutralizing antibody titres than did oral placebo booster. A single oral booster following two subcutaneous priming doses elicited serum IgG and mucosal IgA levels similar to those raised by three subcutaneous doses. In conclusion, the oral LTB-adjuvanted multi-epitope SARS-CoV-2 vaccine triggered versatile humoral, cellular and mucosal immune responses, which are likely to provide protection, while also minimizing technical hurdles presently limiting global vaccination, whether by priming or booster programs.

scholarly journals Dual roles of a novel oncolytic viral vector-based SARS-CoV-2 vaccine: preventing COVID-19 and treating tumor progression

2021 ◽  
Author(s):  
Michael A. Caligiuri ◽  
Jianhua Yu ◽  
Yaping Sun ◽  
Wenjuan Dong ◽  
Lei Tian ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Viral Vector ◽  
Protein A ◽  
Surface Protein ◽  
T Cell Response ◽  
Host Cells ◽  
Serious Adverse Events ◽  
S Protein ◽  
Tumor Bearing

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer patients are usually immunocompromised and thus are particularly susceptible to SARS-CoV-2 infection resulting in COVID-19. Although many vaccines against COVID-19 are being preclinically or clinically tested or approved, none have yet been specifically developed for cancer patients or reported as having potential dual functions to prevent COVID-19 and treat cancer. Here, we confirmed that COVID-19 patients with cancer have low levels of antibodies against the spike (S) protein, a viral surface protein mediating the entry of SARS-CoV-2 into host cells, compared with COVID-19 patients without cancer. We developed an oncolytic herpes simplex virus-1 vector-based vaccine named oncolytic virus (OV)-spike. OV-spike induced abundant anti-S protein neutralization antibodies in both tumor-free and tumor-bearing mice, which inhibit infection of VSV-SARS-CoV-2 and wild-type (WT) live SARS-CoV-2 as well as the B.1.1.7 variant in vitro. In the tumor-bearing mice, OV-spike also inhibited tumor growth, leading to better survival in multiple preclinical tumor models than the untreated control. Furthermore, OV-spike induced anti-tumor immune response and SARS-CoV-2-specific T cell response without causing serious adverse events. Thus, OV-spike is a promising vaccine candidate for both preventing COVID-19 and enhancing the anti-tumor response.

scholarly journals Reservoir Targeted Vaccine for Lyme Borreliosis Induces a Yearlong, Neutralizing Antibody Response to OspA in White-Footed Mice

2011 ◽  
Vol 18 (11) ◽  
pp. 1809-1816 ◽  
Author(s):  
Luciana Meirelles Richer ◽  
Miguel Aroso ◽  
Tania Contente-Cuomo ◽  
Larisa Ivanova ◽  
Maria Gomes-Solecki
Keyword(s):  
Immune Response ◽  
Lyme Disease ◽  
Protein A ◽  
Surface Protein ◽  
Neutralizing Antibody ◽  
Control Measures ◽  
Content Type ◽  
Wildlife Reservoirs ◽  
Minimum Number ◽  
Enzootic Cycle

ABSTRACTLyme disease is caused by the spirocheteBorrelia burgdorferi. The enzootic cycle of this pathogen requires thatIxodesspp. acquireB. burgdorferifrom infected wildlife reservoirs and transmit it to other uninfected wildlife. At present, there are no effective measures to controlB. burgdorferi; there is no human vaccine available, and existing vector control measures are generally not acceptable to the public. However, ifB. burgdorfericould be eliminated from its reservoir hosts or from the ticks that feed on them, the enzootic cycle would be broken, and the incidence of Lyme disease would decrease. We developed OspA-RTV, a reservoir targeted bait vaccine (RTV) based on the immunogenic outer surface protein A (OspA) ofB. burgdorferiaimed at breaking the natural cycle of this spirochete. White-footed mice, the major reservoir species for this spirochete in nature developed a systemic OspA-specific IgG response as a result of ingestion of the bait formulation. This immune response protected white-footed mice againstB. burgdorferiinfection upon tick challenge and clearedB. burgdorferifrom the tick vector. In performing extensive studies to optimize the OspA-RTV for field deployment, we determined that mice that consumed the vaccine over periods of 1 or 4 months developed a yearlong, neutralizing anti-OspA systemic IgG response. Furthermore, we defined the minimum number of OspA-RTV units needed to induce a protective immune response.

scholarly journals Characterization of Protective Mucosal and Systemic Immune Responses Elicited by Pneumococcal Surface Protein PspA and PspC Nasal Vaccines against a Respiratory Pneumococcal Challenge in Mice

2009 ◽  
Vol 16 (5) ◽  
pp. 636-645 ◽  
Author(s):  
D. M. Ferreira ◽  
M. Darrieux ◽  
D. A. Silva ◽  
L. C. C. Leite ◽  
J. M. C. Ferreira ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protein A ◽  
Surface Protein ◽  
Interleukin 17 ◽  
Necrosis Factor Alpha ◽  
Pneumococcal Strain ◽  
Mucosal Vaccines ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Pneumococcal surface protein A (PspA) and PspC are virulence factors that are involved in the adhesion of Streptococcus pneumoniae to epithelial cells and/or evasion from the immune system. Here, the immune responses induced by mucosal vaccines composed of both antigens as recombinant proteins or delivered by Lactobacillus casei were evaluated. None of the PspC vaccines protected mice against an invasive challenge with pneumococcal strain ATCC 6303. On the other hand, protection was observed for immunization with vaccines composed of PspA from clade 5 (PspA5 or L. casei expressing PspA5) through the intranasal route. The protective response was distinguished by a Th1 profile with high levels of immunoglobulin G2a production, efficient complement deposition, release of proinflammatory cytokines, and infiltration of neutrophils. Intranasal immunization with PspA5 elicited the highest level of protection, characterized by increased levels of secretion of interleukin-17 and gamma interferon by lung and spleen cells, respectively, and low levels of tumor necrosis factor alpha in the respiratory tract.

Pneumococcal Surface Protein A does not affect the immune responses to a combined diphtheria tetanus and pertussis vaccine in mice

Vaccine ◽  
2013 ◽  
Vol 31 (20) ◽  
pp. 2465-2470 ◽  
Author(s):  
Fernanda A. Lima ◽  
Eliane N. Miyaji ◽  
Wagner Quintilio ◽  
Isaias Raw ◽  
Paulo L. Ho ◽  
...  
Keyword(s):  
Immune Responses ◽  
Pertussis Vaccine ◽  
Protein A ◽  
Surface Protein ◽  
Pneumococcal Surface Protein A

scholarly journals Different Profiles of Antibodies and Cytokines Were Found Between Severe and Moderate COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Yaolin Guo ◽  
Tianyi Li ◽  
Xinyi Xia ◽  
Bin Su ◽  
Hanping Li ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Healthy Individuals ◽  
S Protein ◽  
Elisa System ◽  
N Protein ◽  
Tnf Α ◽  
Significant Difference ◽  
Positive Rate ◽  
Antibody Titers ◽  
Ifn Γ

ObjectivesOur objective was to determine the antibody and cytokine profiles in different COVID-19 patients.MethodsCOVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests.ResultsA total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody.ConclusionsOur findings show the severe COVID-19 patients’ antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.

scholarly journals Pneumococcal Surface Protein A: A Promising Candidate for the Next Generation of Pneumococcal Vaccines

2022 ◽  
Vol 67 (4) ◽  
pp. 289-298
Author(s):  
Saad Alghamdi ◽  
Muhammad Umar Khayam Sahibzada ◽  
Nashwa T. Shesha ◽  
Akhmed Aslam ◽  
Ahmed Kabrah ◽  
...  
Keyword(s):  
Immune Responses ◽  
Pneumococcal Disease ◽  
Vaccine Candidate ◽  
Protein A ◽  
Surface Protein ◽  
Pneumococcal Infections ◽  
Promising Candidate ◽  
Host Immune Responses ◽  
Pneumococcal Surface Protein A ◽  
Potential Vaccine

Streptococcus pneumoniae is the bacterium that causes pneumococcal disease which often results in pneumonia, meningitis, otitis media, septicemia and sinusitis. Pneumonia, particularly, is a significant cause of worldwide morbidity and a global health burden as well. Treatment often relies on antimicrobials, to which the pathogen is frequently mutating and rendering infective. Consequently, vaccination is the most effective approach in dealing with pneumococcal antimicrobial resistance (AMR). Unfortunately, the current pneumococcal polysaccharide and conjugate vaccines have a narrow serotype coverage. Therefore, the current need for vaccines with a broader serotype coverage cannot be overstated. Pneumococcal Surface Protein A and C are potential vaccine candidate antigens present in over 90% of the strains from clinical isolates as well as laboratory non-encapsulated strains. Pneumococcal Surface Protein A is an active virulent factor that pneumococci use to evade complement-mediated host immune responses and has been shown to elicit immune responses against pneumococcal infections. This review explores the potential utilization of Pneumococcal Surface Protein A to immunize against S. pneumoniae.

scholarly journals Genetic Alteration of Capsule Type but Not PspA Type Affects Accessibility of Surface-Bound Complement and Surface Antigens of Streptococcus pneumoniae

2003 ◽  
Vol 71 (1) ◽  
pp. 218-225 ◽  
Author(s):  
Melanie Abeyta ◽  
Gail G. Hardy ◽  
Janet Yother
Keyword(s):  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Protein A ◽  
Surface Protein ◽  
Surface Antigens ◽  
Capsular Polysaccharides ◽  
Capsule Type ◽  
Type 3 ◽  
Determining Factor

ABSTRACT The Streptococcus pneumoniae capsular polysaccharides and pneumococcal surface protein A (PspA) are major determinants of virulence that are antigenically variable and capable of eliciting protective immune responses. By genetically switching the pspA genes of the capsule type 2 strain D39 and the capsule type 3 strain WU2, we showed that the different abilities of antibody to PspA to protect against these strains was not related to the PspA type expressed. Similarly, the level of specific antibody binding to PspA, other surface antigens, and surface-localized C3b did not depend on the PspA type but instead was correlated with the capsule type. The type 3 strain WU2 and an isogenic derivative of D39 that expresses the type 3 capsule bound nearly identical amounts of antibody to PspA and other surface antigens, and these amounts were less than one-half the amount observed with the type 2 parent strain D39. Expression of the type 3 capsule in D39 also reduced the amount of C3b deposited and its accessibility to antibody, resulting in a level intermediate between the levels observed with WU2 and D39. Despite these effects, the capsule type was not the determining factor in anti-PspA-mediated protection, as both D39 and its derivative expressing the type 3 capsule were more resistant to protection than WU2. The specific combination of PspA and capsule type also did not determine the level of protection. The capsule structure is thus a major determinant in accessibility of surface antigens to antibody, but certain strains appear to express other factors that can influence antibody-mediated protection.

PsaA (pneumococcal surface adhesin A) and PspA (pneumococcal surface protein A) DNA vaccines induce humoral and cellular immune responses against Streptococcus pneumoniae

Vaccine ◽  
2001 ◽  
Vol 20 (5-6) ◽  
pp. 805-812 ◽  
Author(s):  
Eliane N. Miyaji ◽  
Waldely O. Dias ◽  
Márcia Gamberini ◽  
Vera C.B.C. Gebara ◽  
Rocilda P.F. Schenkman ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Dna Vaccines ◽  
Protein A ◽  
Surface Protein ◽  
Cellular Immune Responses ◽  
Pneumococcal Surface Protein A ◽  
Cellular Immune

scholarly journals SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques

2021 ◽  
Vol 6 (60) ◽  
pp. eabj3684
Author(s):  
Carolina Garrido ◽  
Alan D. Curtis ◽  
Maria Dennis ◽  
Sachi H. Pathak ◽  
Hongmei Gao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Rhesus Macaques ◽  
Pediatric Population ◽  
Neutralizing Antibody ◽  
Socioeconomic Impacts ◽  
S Protein ◽  
Specific Memory ◽  
Vaccine Schedule ◽  
Igg Binding ◽  
Infant Rhesus

The inclusion of infants in the SARS-CoV-2 vaccine roll-out is important to prevent severe complications of pediatric SARS-CoV-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. However, age-dependent differences in immune function require careful evaluation of novel vaccines in the pediatric population. Toward this goal, we assessed the safety and immunogenicity of two SARS-CoV-2 vaccines. Two groups of 8 infant rhesus macaques (RMs) were immunized intramuscularly at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or the purified S protein mixed with 3M-052, a synthetic TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. Both vaccines elicited high magnitude IgG binding to RBD, N terminus domain, S1, and S2, ACE2 blocking activity, and high neutralizing antibody titers, all peaking at week 6. S-specific memory B cells were detected by week 4 and S-specific T cell responses were dominated by the production of IL-17, IFN-γ, or TNF-α. Antibody and cellular responses were stable through week 22. The immune responses for the mRNA-LNP vaccine were of a similar magnitude to those elicited by the Moderna mRNA-1273 vaccine in adults. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines were well-tolerated and highly immunogenic in infant RMs, providing proof-of concept for a pediatric SARS-CoV-2 vaccine with the potential for durable immunity that might decrease the transmission of SARS-CoV-2 and mitigate the ongoing health and socioeconomic impacts of COVID-19.

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