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1.
Front Immunol ; 13: 836745, 2022.
Article in English | MEDLINE | ID: covidwho-1963439

ABSTRACT

Several vaccine candidates for COVID-19 have been developed, and few vaccines received emergency approval with an acceptable level of efficacy and safety. We herein report the development of the first recombinant protein-based vaccine in Iran based on the recombinant SARS-CoV-2 spike protein in its monomeric (encompassing amino acid 1-674 for S1 and 685-1211 for S2 subunits) and trimer form (S-Trimer) formulated in the oil-in-water adjuvant system RAS-01 (Razi Adjuvant System-01). The safety and immunity of the candidate vaccine, referred to as RAZI-COV PARS, were evaluated in Syrian hamster, BALB/c mice, Pirbright guinea pig, and New Zeeland white (NZW) rabbit. All vaccinated animals received two intramuscular (IM) and one intranasal (IN) candidate vaccine at 3-week intervals (days 0, 21, and 51). The challenge study was performed intranasally with 5×106 pfu of SARS-CoV-2 35 days post-vaccination. None of the vaccinated mice, hamsters, guinea pigs, or rabbits showed any changes in general clinical observations; body weight and food intake, clinical indicators, hematology examination, blood chemistry, and pathological examination of vital organs. Safety of vaccine after the administration of single and repeated dose was also established. Three different doses of candidate vaccine stimulated remarkable titers of neutralizing antibodies, S1, Receptor-Binding Domain (RBD), and N-terminal domain (NTD) specific IgG antibodies as well as IgA antibodies compared to placebo and control groups (P<0.01). Middle and high doses of RAZI-COV PARS vaccine significantly induced a robust and quick immune response from the third-week post-immunization. Histopathological studies on vaccinated hamsters showed that the challenge with SARS-CoV-2 did not induce any modifications in the lungs. The protection of the hamster was documented by the absence of lung pathology, the decreased virus load in the lung, rapid clearance of the virus from the lung, and strong humoral and cellular immune response. These findings confirm the immunogenicity and efficacy of the RAZI-COV PARS vaccine. Of the three tested vaccine regimens, the middle dose of the vaccine showed the best protective immune parameters. This vaccine with heterologous prime-boost vaccination method can be a good candidate to control the viral infection and its spread by stimulating central and mucosal immunity.


Subject(s)
COVID-19 Vaccines , COVID-19 , Animals , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Cricetinae , Guinea Pigs , Humans , Mice , Models, Animal , Rabbits , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Combined , Vaccines, Synthetic
2.
Int J Biol Sci ; 18(12): 4781-4791, 2022.
Article in English | MEDLINE | ID: covidwho-1954684

ABSTRACT

Rapid development and successful use of vaccines against SARS-CoV-2 might hold the key to curb the ongoing pandemic of COVID-19. Emergence of vaccine-evasive SARS-CoV-2 variants of concern (VOCs) has posed a new challenge to vaccine design and development. One urgent need is to determine what types of variant-specific and bivalent vaccines should be developed. Here, we compared homotypic and heterotypic protection against SARS-CoV-2 infection of hamsters with monovalent and bivalent whole-virion inactivated vaccines derived from representative VOCs. In addition to the ancestral SARS-CoV-2 Wuhan strain, Delta (B.1.617.2; δ) and Theta (P.3; θ) variants were used in vaccine preparation. Additional VOCs including Omicron (B.1.1.529) and Alpha (B.1.1.7) variants were employed in the challenge experiment. Consistent with previous findings, Omicron variant exhibited the highest degree of immune evasion, rendering all different forms of inactivated vaccines substantially less efficacious. Notably, monovalent and bivalent Delta variant-specific inactivated vaccines provided optimal protection against challenge with Delta variant. Yet, some cross-variant protection against Omicron and Alpha variants was seen with all monovalent and bivalent inactivated vaccines tested. Taken together, our findings support the notion that an optimal next-generation inactivated vaccine against SARS-CoV-2 should contain the predominant VOC in circulation. Further investigations are underway to test whether a bivalent vaccine for Delta and Omicron variants can serve this purpose.


Subject(s)
COVID-19 , Viral Vaccines , Animals , COVID-19/prevention & control , COVID-19 Vaccines , Cricetinae , Humans , SARS-CoV-2 , Vaccines, Combined , Vaccines, Inactivated
3.
J Virol ; 96(15): e0068922, 2022 Aug 10.
Article in English | MEDLINE | ID: covidwho-1949995

ABSTRACT

Vaccines targeting SARS-CoV-2 have been shown to be highly effective; however, the breadth against emerging variants and the longevity of protection remains unclear. Postimmunization boosting has been shown to be beneficial for disease protection, and as new variants continue to emerge, periodic (and perhaps annual) vaccination will likely be recommended. New seasonal influenza virus vaccines currently need to be developed every year due to continual antigenic drift, an undertaking made possible by a robust global vaccine production and distribution infrastructure. To create a seasonal combination vaccine targeting both influenza viruses and SARS-CoV-2 that is also amenable to frequent reformulation, we have developed an influenza A virus (IAV) genetic platform that allows the incorporation of an immunogenic domain of the SARS-CoV-2 spike (S) protein onto IAV particles. Vaccination with this combination vaccine elicited neutralizing antibodies and provided protection from lethal challenge with both pathogens in mice. This approach may allow the leveraging of established influenza vaccine infrastructure to generate a cost-effective and scalable seasonal vaccine solution for both influenza and coronaviruses. IMPORTANCE The rapid emergence of SARS-CoV-2 variants since the onset of the pandemic has highlighted the need for both periodic vaccination "boosts" and a platform that can be rapidly reformulated to manufacture new vaccines. In this work, we report an approach that can utilize current influenza vaccine manufacturing infrastructure to generate combination vaccines capable of protecting from both influenza virus- and SARS-CoV-2-induced disease. The production of a combined influenza/SARS-CoV-2 vaccine may represent a practical solution to boost immunity to these important respiratory viruses without the increased cost and administration burden of multiple independent vaccines.


Subject(s)
COVID-19 , Influenza A virus , Influenza Vaccines , Influenza, Human , Orthomyxoviridae , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Influenza, Human/prevention & control , Mice , SARS-CoV-2 , Vaccines, Combined , Virion
4.
Methods Mol Biol ; 2511: 21-36, 2022.
Article in English | MEDLINE | ID: covidwho-1941364

ABSTRACT

The emergence of new SARS-CoV-2 variants has led to increased transmission and more severe cases of COVID-19, with some having the ability to escape the existing vaccines. This review discusses the importance of developing new vaccine strategies to keep pace with these variants to more effectively manage the pandemic. Many of the new vaccine approaches include multivalent display of the most highly mutated regions in the SARS-CoV-2 spike protein such that they resemble a virus particle and can stimulate an effective neutralization response. It is hoped that such approaches help to manage the existing pandemic and provide a robust infrastructure toward fast tracking responses across the world in case of future pandemics.


Subject(s)
COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Vaccines, Combined , COVID-19/prevention & control , Humans , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics
5.
Front Immunol ; 13: 852904, 2022.
Article in English | MEDLINE | ID: covidwho-1938617

ABSTRACT

OVX836 is a recombinant protein-based vaccine targeting the highly conserved influenza nucleoprotein (NP), which aims to confer a broad-spectrum protection against influenza. In a Phase 1 study, OVX836, administered intramuscularly, has been found safe and immunogenic. The 90µg and 180µg dose levels were selected to be further evaluated in this randomized, monocenter, reference-controlled (Influvac Tetra™: quadrivalent seasonal influenza subunit vaccine), parallel group, double-blind, Phase 2a study in 300 healthy volunteers, aged 18-65 years, during the 2019/2020 flu season. Safety, influenza-like illness episodes (ILI; based on the Flu-PRO® questionnaire) and immunogenicity were assessed up to 180 days post-vaccination. OVX836 was safe and presented a reactogenicity profile similar to Influvac Tetra. It induced a significant increase in terms of NP-specific interferon-gamma (IFNγ) spot forming cells (SFCs), NP-specific CD4+ T-cells (essentially polyfunctional cells) and anti-NP IgG responses. OVX836 was superior to Influvac Tetra for all immunological parameters related to NP, and the 180µg dose was significantly superior to the 90µg dose for SFCs and CD4+ T-cells expressing IFNγ. Both the CD4+ T-cell and the anti-NP IgG responses persisted up to Day 180. An efficacy signal was observed with OVX836 at 180µg through reduction of ILI episodes occurring during the flu season as of 14 days post-vaccination. In conclusion, these results encourage further clinical evaluation of OVX836 in order to confirm the signal of efficacy on ILIs and/or laboratory-confirmed influenza cases. NCT04192500 (https://clinicaltrials.gov/ct2/show/study/NCT04192500).


Subject(s)
Influenza Vaccines , Influenza, Human , Adolescent , Adult , Aged , Double-Blind Method , Humans , Immunoglobulin G , Influenza Vaccines/adverse effects , Influenza, Human/prevention & control , Interferon-gamma , Middle Aged , Nucleoproteins , Vaccines, Combined , Vaccines, Synthetic , Young Adult
6.
Front Immunol ; 13: 863234, 2022.
Article in English | MEDLINE | ID: covidwho-1903009

ABSTRACT

Mucormycosis is a potentially fatal illness that arises in immunocompromised people due to diabetic ketoacidosis, neutropenia, organ transplantation, and elevated serum levels of accessible iron. The sudden spread of mucormycosis in COVID-19 patients engendered massive concern worldwide. Comorbidities including diabetes, cancer, steroid-based medications, long-term ventilation, and increased ferritin serum concentration in COVID-19 patients trigger favorable fungi growth that in turn effectuate mucormycosis. The necessity of FTR1 gene-encoded ferrous permease for host iron acquisition by fungi has been found in different studies recently. Thus, targeting the transit component could be a potential solution. Unfortunately, no appropriate antifungal vaccine has been constructed as of yet. To date, mucormycosis has been treated with antiviral therapy and surgical treatment only. Thus, in this study, the FTR1 protein has been targeted to design a convenient and novel epitope-based vaccine with the help of immunoinformatics against four different virulent fungal species. Furthermore, the vaccine was constructed using 8 CTL, 2 HTL, and 1 LBL epitopes that were found to be highly antigenic, non-allergenic, non-toxic, and fully conserved among the fungi under consideration. The vaccine has very reassuring stability due to its high pI value of 9.97, conclusive of a basic range. The vaccine was then subjected to molecular docking, molecular dynamics, and immune simulation studies to confirm the biological environment's safety, efficacy, and stability. The vaccine constructs were found to be safe in addition to being effective. Finally, we used in-silico cloning to develop an effective strategy for vaccine mass production. The designed vaccine will be a potential therapeutic not only to control mucormycosis in COVID-19 patients but also be effective in general mucormycosis events. However, further in vitro, and in vivo testing is needed to confirm the vaccine's safety and efficacy in controlling fungal infections. If successful, this vaccine could provide a low-cost and effective method of preventing the spread of mucormycosis worldwide.


Subject(s)
COVID-19 , Mucormycosis , COVID-19/prevention & control , Epitopes, B-Lymphocyte , Epitopes, T-Lymphocyte , Fungi , Humans , Iron/metabolism , Molecular Docking Simulation , Mucormycosis/microbiology , Mucormycosis/prevention & control , SARS-CoV-2 , Vaccines, Combined , Vaccines, Subunit
7.
Int J Mol Sci ; 23(11)2022 May 30.
Article in English | MEDLINE | ID: covidwho-1869639

ABSTRACT

The SARS-CoV-2 pandemic has created a global public crisis and heavily affected personal lives, healthcare systems, and global economies. Virus variants are continuously emerging, and, thus, the pandemic has been ongoing for over two years. Vaccines were rapidly developed based on the original SARS-CoV-2 (Wuhan-Hu-1) to build immunity against the coronavirus disease. However, they had a very low effect on the virus' variants due to their low cross-reactivity. In this study, a multivalent SARS-CoV-2 vaccine was developed using ferritin nanocages, which display the spike protein from the Wuhan-Hu-1, B.1.351, or B.1.429 SARS-CoV-2 on their surfaces. We show that the mixture of three SARS-CoV-2 spike-protein-displaying nanocages elicits CD4+ and CD8+ T cells and B-cell immunity successfully in vivo. Furthermore, they generate a more consistent antibody response against the B.1.351 and B.1.429 variants than a monovalent vaccine. This leads us to believe that the proposed ferritin-nanocage-based multivalent vaccine platform will provide strong protection against emerging SARS-CoV-2 variants of concern (VOCs).


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing/genetics , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , COVID-19 Vaccines , Ferritins/genetics , Humans , Immunity , Mutation , SARS-CoV-2 , Vaccines, Combined
8.
J Med Virol ; 94(9): 4287-4293, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1864337

ABSTRACT

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, sublineages BA.1 and BA.2, recently became the dominant variants of concern (VOCs) with significantly higher transmissibility than any other variant appeared and markedly greater resistance to neutralization antibodies and original ancestral WA1 spike-matched vaccine. Therefore, it is urgent to develop vaccines against VOCs like Omicron. Unlike the new booming messenger RNA (mRNA) vaccine, protein vaccines have been used for decades to protect people from various kinds of viral infections and have advantages with their inexpensive production protocols and their relative stability in comparison to the mRNA vaccine. Here, we show that sera from BA.1 spike protein vaccinated mice mainly elicited neutralizing antibodies against BA.1 itself. However, a booster with BA.1 spike protein or a bivalent vaccine composed of D614G and BA.1 spike protein-induced not only potent neutralizing antibody response against D614G and BA.1 pseudovirus, but also against BA.2, other four SARS-CoV-2 VOCs (Alpha, Beta, Gamma, and Delta) and SARS-CoV-2-related coronaviruses (pangolin CoV GD-1 and bat CoV RsSHC014). The two recombinant spike protein vaccines method described here lay a foundation for future vaccine development for broad protection against pan-sarbecovirus.


Subject(s)
COVID-19 Vaccines , COVID-19 , Spike Glycoprotein, Coronavirus , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Humans , Mice , Mice, Inbred BALB C , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Combined , Vaccines, Synthetic/immunology , mRNA Vaccines/immunology
9.
Front Immunol ; 13: 884433, 2022.
Article in English | MEDLINE | ID: covidwho-1862609

ABSTRACT

The development of an effective multivalent vaccine against SARS-CoV-2 variants is an important means to improve the global public health situation caused by COVID-19. In this study, we identified the antigen epitopes of the main global epidemic SARS-CoV-2 and mutated virus strains using immunoinformatics approach, and screened out 8 cytotoxic T lymphocyte epitopes (CTLEs), 17 helper T lymphocyte epitopes (HTLEs), 9 linear B-cell epitopes (LBEs) and 4 conformational B-cell epitopes (CBEs). The global population coverage of CTLEs and HTLEs was 93.16% and 99.9% respectively. These epitopes were spliced together by corresponding linkers and recombined into multivalent vaccine. In silico tests, the vaccine protein was a non-allergen and the docking with TLR-3 molecule showed a strong interaction. The results of immune simulation showed that the vaccine may be helpful to initiate both cellular and humoral immunity against all VOC. The optimistic immunogenicity of the vaccine was confirmed in vivo and in vitro finally. Therefore, our vaccine may have potential protection against SARS-CoV-2 and its variants.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevention & control , COVID-19 Vaccines , Epitopes, B-Lymphocyte/genetics , Epitopes, T-Lymphocyte/genetics , Humans , Molecular Docking Simulation , SARS-CoV-2/genetics , Vaccines, Combined
10.
Comp Immunol Microbiol Infect Dis ; 86: 101803, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1767978

ABSTRACT

In many countries, vaccination programs still require dogs to be vaccinated against rabies in addition to Canine distemper virus (CDV), adenovirus (CAV), parvovirus (CPV), parainfluenza virus (CPiV), Leptospira (L) or Canine coronavirus (CCV= Cv). Few vaccines containing all these antigens are commercially available and, unless compatibility between the vaccines was demonstrated, concurrent administration of a DAPPi-L(Cv) vaccine and a vaccine against rabies should not be recommended. This may be of concern for practitioners who wish to vaccinate dogs with all components on the same day. This study aimed at evaluating immunological compatibility between a monovalent rabies vaccine (Rabisin™) and two large combination vaccines against CDV, CAV, CPV, CPiV with 2 leptospira components +Cv (Recombitek® C6/Cv) or with 4 Leptospira components (Recombitek® C8), when injected concomitantly at two separate injection sites. Fourteen days after administration of the rabies vaccine, with or without concomitant administration of combo vaccines, all dogs had seroconverted against rabies and maintained protective titers over the duration of the study. In addition, 100% of the puppies vaccinated with one or the other combo vaccines seroconverted against CDV, CAV, CPV, CPiV (CCV) and Leptospira, whatever the vaccination group. Lack of immunological interference between Rabisin™ and all components of the Recombitek® C6/Cv or Recombitek® C8 Combo vaccines was demonstrated by non-inferiority analysis, except for CDV in the Recombitek®C8+ Rabisin™ group. Based on these results, a concomitant administration of Rabisin™ with Recombitek® C6/Cv or Recombitek® C8 can be recommended in daily practice, which can be essential for facilitating vaccination compliance.


Subject(s)
Coronavirus, Canine , Distemper Virus, Canine , Distemper , Dog Diseases , Leptospira , Leptospirosis , Parvovirus, Canine , Rabies Vaccines , Rabies , Viral Vaccines , Animals , Antibodies, Viral , Distemper/prevention & control , Dogs , Leptospirosis/veterinary , Rabies/prevention & control , Rabies/veterinary , Vaccines, Combined
11.
Cell Rep ; 38(3): 110256, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1588136

ABSTRACT

Inoculation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing worldwide. However, the emergence of SARS-CoV-2 variants could cause immune evasion. We developed a bivalent nanoparticle vaccine that displays the receptor binding domains (RBDs) of the D614G and B.1.351 strains. With a prime-boost or a single-dose strategy, this vaccine elicits a robust neutralizing antibody and full protection against infection with the authentic D614G or B.1.351 strain in human angiotensin-converting enzyme 2 transgene mice. Interestingly, 8 months after inoculation with the D614G-specific vaccine, a new boost with this bivalent vaccine potently elicits cross-neutralizing antibodies for SARS-CoV-2 variants in rhesus macaques. We suggest that the D614G/B.1.351 bivalent vaccine could be used as an initial single dose or a sequential enforcement dose to prevent infection with SARS-CoV-2 and its variants.


Subject(s)
COVID-19/prevention & control , Cross Protection , SARS-CoV-2/immunology , Vaccines, Combined/therapeutic use , Animals , CHO Cells , COVID-19 Vaccines/chemical synthesis , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Chlorocebus aethiops , Cricetulus , Cross Protection/immunology , Female , HEK293 Cells , Humans , Macaca mulatta , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Nanoparticles , Vaccination/methods , Vaccines, Combined/chemical synthesis , Vaccines, Combined/immunology , Vero Cells
12.
Front Immunol ; 12: 692937, 2021.
Article in English | MEDLINE | ID: covidwho-1403473

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kills thousands of people worldwide every day, thus necessitating rapid development of countermeasures. Immunoinformatics analyses carried out here in search of immunodominant regions in recently identified SARS-CoV-2 unannotated open reading frames (uORFs) have identified eight linear B-cell, one conformational B-cell, 10 CD4+ T-cell, and 12 CD8+ T-cell promising epitopes. Among them, ORF9b B-cell and T-cell epitopes are the most promising followed by M.ext and ORF3c epitopes. ORF9b40-48 (CD8+ T-cell epitope) is found to be highly immunogenic and antigenic with the highest allele coverage. Furthermore, it has overlap with four potent CD4+ T-cell epitopes. Structure-based B-cell epitope prediction has identified ORF9b61-68 to be immunodominant, which partially overlaps with one of the linear B-cell epitopes (ORF9b65-69). ORF3c CD4+ T-cell epitopes (ORF3c2-16, ORF3c3-17, and ORF3c4-18) and linear B-cell epitope (ORF3c14-22) have also been identified as the candidate epitopes. Similarly, M.ext and 7a.iORF1 (overlap with M and ORF7a) proteins have promising immunogenic regions. By considering the level of antigen expression, four ORF9b and five M.ext epitopes are finally shortlisted as potent epitopes. Mutation analysis has further revealed that the shortlisted potent uORF epitopes are resistant to recurrent mutations. Additionally, four N-protein (expressed by canonical ORF) epitopes are found to be potent. Thus, SARS-CoV-2 uORF B-cell and T-cell epitopes identified here along with canonical ORF epitopes may aid in the design of a promising epitope-based polyvalent vaccine (when connected through appropriate linkers) against SARS-CoV-2. Such a vaccine can act as a bulwark against SARS-CoV-2, especially in the scenario of emergence of variants with recurring mutations in the spike protein.


Subject(s)
Antigens, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Coronavirus Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Amino Acid Sequence/genetics , Antigens, Viral/genetics , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/genetics , COVID-19 Vaccines/therapeutic use , Computational Biology , Coronavirus Nucleocapsid Proteins/genetics , Drug Design , Epitope Mapping , Epitopes, B-Lymphocyte/genetics , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , Humans , Open Reading Frames/genetics , Open Reading Frames/immunology , SARS-CoV-2/genetics , Sequence Analysis, Protein , Vaccines, Combined/genetics , Vaccines, Combined/immunology
13.
Signal Transduct Target Ther ; 6(1): 278, 2021 07 17.
Article in English | MEDLINE | ID: covidwho-1387234
14.
Biomed Res Int ; 2021: 9940010, 2021.
Article in English | MEDLINE | ID: covidwho-1259034

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) infection is a public health epidemic, leading to around 3 million hospitalization and about 66,000 deaths each year. It is a life-threatening condition exclusive to children with no effective treatment. METHODS: In this study, we used system-level and vaccinomics approaches to design a polyvalent vaccine for RSV, which could stimulate the immune components of the host to manage this infection. Our framework involves data accession, antigenicity and subcellular localization analysis, T cell epitope prediction, proteasomal and conservancy evaluation, host-pathogen-protein interactions, pathway studies, and in silico binding affinity analysis. RESULTS: We found glycoprotein (G), fusion protein (F), and small hydrophobic protein (SH) of RSV as potential vaccine candidates. Of these proteins (G, F, and SH), we found 9 epitopes for multiple alleles of MHC classes I and II bear significant binding affinity. These potential epitopes were linked to form a polyvalent construct using AAY, GPGPG linkers, and cholera toxin B adjuvant at N-terminal with a 23.9 kDa molecular weight of 224 amino acid residues. The final construct was a stable, immunogenic, and nonallergenic protein containing cleavage sites, TAP transport efficiency, posttranslation shifts, and CTL epitopes. The molecular docking indicated the optimum binding affinity of RSV polyvalent construct with MHC molecules (-12.49 and -10.48 kcal/mol for MHC classes I and II, respectively). This interaction showed that a polyvalent construct could manage and control this disease. CONCLUSION: Our vaccinomics and system-level investigation could be appropriate to trigger the host immune system to prevent RSV infection.


Subject(s)
Computational Biology/methods , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus, Human , Vaccines, Combined/therapeutic use , Alleles , Antigens , Codon , Computer Simulation , Epitopes , Epitopes, T-Lymphocyte , Glycoproteins/chemistry , Histocompatibility Antigens Class I , Histocompatibility Antigens Class II , Hospitalization , Humans , Immune System , Molecular Docking Simulation , Proteasome Endopeptidase Complex , Protein Interaction Mapping , Proteomics , T-Lymphocytes/immunology , Vaccines , Viral Fusion Proteins/chemistry
15.
Arch Argent Pediatr ; 119(3): 198-201, 2021 06.
Article in English, Spanish | MEDLINE | ID: covidwho-1242313

ABSTRACT

INTRODUCTION: The reduction in the number of visits to health care centers since the onset of the SARS-CoV-2 pandemic may affect mandatory vaccination. OBJECTIVE: To assess the impact of the SARS-CoV-2 pandemic on the administration of the pentavalent and the measles, mumps, and rubella (MMR) vaccines to children younger than 2 years at the vaccination center of a children's hospital in the Autonomous City of Buenos Aires. METHOD: Cross-sectional study using the vaccination center's digital records from January to May 2019 and 2020. Results. In the second fortnight of March 2020, vaccinations dropped by 64.2 %. When examining the first dose of the pentavalent and MMR vaccines, such reduction was 74.9 % and 55.1 %, respectively. CONCLUSION: As of the second fortnight of March 2020, vaccinations dropped by 64.2 % compared to the same period of the previous year.


Introducción. El menor número de consultas a los centros de atención desde el comienzo de la pandemia por SARS-CoV-2 podría afectar la vacunación obligatoria. Objetivo. Evaluar el impacto de la pandemia por SARS-CoV-2 en la administración de vacunas pentavalente y triple viral a niños menores de 2 años en el vacunatorio de un hospital pediátrico de la Ciudad de Buenos Aires. Método. Estudio transversal, que utilizó registros informatizados del vacunatorio, de enero a mayo de 2019 y 2020. Resultados. Desde la segunda quincena de marzo de 2020, se observó un 64,2 % de disminución en la aplicación de vacunas. Al examinar la primera dosis de pentavalente y triple viral, la reducción fue del 74,9 % y del 55,1 %, respectivamente. Conclusión. A partir de la segunda quincena de marzo de 2020, se observó una disminución del 64,2 % en las vacunas aplicadas respecto del mismo período en el año anterior.


Subject(s)
COVID-19/prevention & control , Health Services Accessibility/trends , Immunization Schedule , Patient Acceptance of Health Care/statistics & numerical data , Vaccination Coverage/trends , Vaccines, Combined , Argentina/epidemiology , COVID-19/epidemiology , Cross-Sectional Studies , Female , Health Policy , Humans , Infant , Infant, Newborn , Male , Pandemics , Physical Distancing
16.
Commun Biol ; 4(1): 597, 2021 05 19.
Article in English | MEDLINE | ID: covidwho-1236095

ABSTRACT

The COVID-19 pandemic continues to wreak havoc as worldwide SARS-CoV-2 infection, hospitalization, and death rates climb unabated. Effective vaccines remain the most promising approach to counter SARS-CoV-2. Yet, while promising results are emerging from COVID-19 vaccine trials, the need for multiple doses and the challenges associated with the widespread distribution and administration of vaccines remain concerns. Here, we engineered the coat protein of the MS2 bacteriophage and generated nanoparticles displaying multiple copies of the SARS-CoV-2 spike (S) protein. The use of these nanoparticles as vaccines generated high neutralizing antibody titers and protected Syrian hamsters from a challenge with SARS-CoV-2 after a single immunization with no infectious virus detected in the lungs. This nanoparticle-based vaccine platform thus provides protection after a single immunization and may be broadly applicable for protecting against SARS-CoV-2 and future pathogens with pandemic potential.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/immunology , COVID-19/prevention & control , Pandemics , SARS-CoV-2 , Animals , Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Drug Delivery Systems , Female , Humans , Immunization/methods , Levivirus/genetics , Levivirus/immunology , Mesocricetus , Microscopy, Electron, Transmission , Models, Animal , Nanoparticles/administration & dosage , Nanoparticles/ultrastructure , Nanotechnology , Pandemics/prevention & control , Protein Engineering , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/administration & dosage , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Combined/administration & dosage , Vaccines, Combined/genetics , Vaccines, Combined/immunology , Vaccines, Virus-Like Particle/administration & dosage , Vaccines, Virus-Like Particle/genetics , Vaccines, Virus-Like Particle/immunology
17.
Infect Genet Evol ; 89: 104712, 2021 04.
Article in English | MEDLINE | ID: covidwho-1196742

ABSTRACT

An immunoinformatics-based approach was used to identify potential multivalent subunit CTL vaccine candidates for SARS-CoV-2. Criteria for computational screening included antigen processing, antigenicity, allergenicity, and toxicity. A total of 2604 epitopes were found to be strong binders to MHC class I molecules when analyzed using IEDB tools. Further testing for antigen processing yielded 826 peptides of which 451 were 9-mers that were analyzed for potential antigenicity. Antigenic properties were predicted for 102 of the 451 peptides. Further assessment for potential allergenicity and toxicity narrowed the number of candidate CTL epitopes to 50 peptide sequences, 45 of which were present in all strains of SARS-CoV-2 that were tested. The predicted CTL epitopes were then tested to eliminate those with MHC class II binding potential, a property that could induce hyperinflammatory responses mediated by TH2 cells in immunized hosts. Eighteen of the 50 epitopes did not show class II binding potential. To our knowledge this is the first comprehensive analysis on the proteome of SARS-CoV-2 for prediction of CTL epitopes lacking binding properties that could stimulate unwanted TH2 responses. Future studies will be needed to assess these epitopes as multivalent subunit vaccine candidates which stimulate protective CTL responses against SARS-COV-2.


Subject(s)
COVID-19 Vaccines/immunology , Epitopes, T-Lymphocyte/immunology , Vaccines, Combined/immunology , Vaccines, Subunit/immunology , Amino Acid Sequence , COVID-19/prevention & control , Epitopes, T-Lymphocyte/chemistry , Histocompatibility Antigens Class I/immunology , Histocompatibility Antigens Class II/immunology , Humans , Immunogenicity, Vaccine/immunology , Molecular Docking Simulation , Proteomics/methods , T-Lymphocytes, Cytotoxic/immunology
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