Immunity to Sda1 Protects against Infection by Sda1+ and Sda1− Serotypes of Group A Streptococcus

Group A Streptococcus (GAS) causes a variety of diseases globally. The DNases in GAS promote GAS evasion of neutrophil killing by degrading neutrophil extracellular traps (NETs). Sda1 is a prophage-encoded DNase associated with virulent GAS strains. However, protective immunity against Sda1 has not been determined. In this study, we explored the potential of Sda1 as a vaccine candidate. Sda1 was used as a vaccine to immunize mice intranasally. The effect of anti-Sda1 IgG in neutralizing degradation of NETs was determined and the protective role of Sda1 was investigated with intranasal and systemic challenge models. Antigen-specific antibodies were induced in the sera and pharyngeal mucosal site after Sda1 immunization. The anti-Sda1 IgG efficiently prevented degradation of NETs by supernatant samples from different GAS serotypes with or without Sda1. Sda1 immunization promoted clearance of GAS from the nasopharynx independent of GAS serotypes but did not reduce lethality after systemic GAS challenge. Anti-Sda1 antibody can neutralize degradation of NETs by Sda1 and other phage-encoded DNases and decrease GAS colonization at the nasopharynx across serotypes. These results indicate that Sda1 can be a potential vaccine candidate for reduction in GAS reservoir and GAS tonsillitis-associated diseases.

Next-Generation Technologies and Systems Biology for the Design of Novel Vaccines Against Apicomplexan Parasites

Parasites of the phylum Apicomplexa are the causative agents of important diseases such as malaria, toxoplasmosis or cryptosporidiosis in humans, and babesiosis and coccidiosis in animals. Whereas the first human recombinant vaccine against malaria has been approved and recently recommended for wide administration by the WHO, most other zoonotic parasitic diseases lack of appropriate immunoprophylaxis. Sequencing technologies, bioinformatics, and statistics, have opened the “omics” era into apicomplexan parasites, which has led to the development of systems biology, a recent field that can significantly contribute to more rational design for new vaccines. The discovery of novel antigens by classical approaches is slow and limited to very few antigens identified and analyzed by each study. High throughput approaches based on the expansion of the “omics”, mainly genomics and transcriptomics have facilitated the functional annotation of the genome for many of these parasites, improving significantly the understanding of the parasite biology, interactions with the host, as well as virulence and host immune response. Developments in genetic manipulation in apicomplexan parasites have also contributed to the discovery of new potential vaccine targets. The present minireview does a comprehensive summary of advances in “omics”, CRISPR/Cas9 technologies, and in systems biology approaches applied to apicomplexan parasites of economic and zoonotic importance, highlighting their potential of the holistic view in vaccine development.

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

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.

Peptide Multimerization as Leads for Therapeutic Development

Multimerization of peptide structures has been a logical evolution in their development as potential therapeutic molecules. The multivalent properties of these assemblies have attracted much attention from researchers in the past and the development of more complex branching dendrimeric structures, with a wide array of biocompatible building blocks is revealing previously unseen properties and activities. These branching multimer and dendrimer structures can induce greater effect on cellular targets than monomeric forms and act as potent antimicrobials, potential vaccine alternatives and promising candidates in biomedical imaging and drug delivery applications. This review aims to outline the chemical synthetic innovations for the development of these highly complex structures and highlight the extensive capabilities of these molecules to rival those of natural biomolecules.

A Multi-Epitope Vaccine Designed Against Blood-Stage of Malaria: An Immunoinformatic And Structural Approach

Malaria is a complex disease caused by genus Plasmodiumis parasites and is the leading cause of morbidity and mortality worldwide. The most severe form of malaria disease is caused by Plasmodium falciparum. A combination of different approaches is needed to control malaria, and on the other hand, resistance to first-line drugs and insecticides makes the need for an effective vaccine more mandatory than ever. Erythrocyte parasites have the most clinical symptoms, so designing the potential vaccine for this stage of infection could be very helpful. In this research, we used various bioinformatics tools to design an effective antibody-inducing multi-epitope vaccine against the blood-stage of malaria infection. For this purpose, we selected the malaria PfGARP protein as the target here. The predicted B and HTL epitopes and flagellin molecule (as an adjuvant) were connected with suitable linkers and the final construct vaccine was designed. The various properties of this construct, including physicochemical properties, 3D structures, molecular docking, molecular simulations, and in silico cloning were then carried out. Based on preliminary findings, our designed fusion construct could be proposed as a novel potential vaccine candidate against Malaria. However, in vitro and in vivo studies are essential for further validation.

Characterization of a Novel Cysteine Protease Inhibitor from Poultry Red Mites: Potential Vaccine for Chickens

Poultry red mite (PRM; Dermanyssus gallinae) is a hazardous, blood-sucking ectoparasite of birds that constitutes a threat to poultry farming worldwide. Acaricides, commonly used in poultry farms to prevent PRMs, are not effective because of the rapid emergence of acaricide-resistant PRMs. However, vaccination may be a promising strategy to control PRM. We identified a novel cystatin-like molecule in PRMs: Dg-Cys. Dg-Cys mRNA expression was detected in the midgut and ovaries, in all stages of life. The PRM nymphs that were artificially fed with the plasma from chickens that were immunized with Dg-Cys in vitro had a significantly reduced reproductive capacity and survival rate. Moreover, combination of Dg-Cys with other antigen candidates, like copper transporter 1 or adipocyte plasma membrane-associated protein, enhanced vaccine efficacies. vaccination and its application as an antigen for cocktail vaccines could be an effective strategy to reduce the damage caused by PRMs in poultry farming.

Complete Genome Sequencing of the Attenuated Strain Mycoplasma synoviae 5-9

Here, we present the complete genome sequence of Mycoplasma synoviae strain 5-9. Strain 5-9 was attenuated by chemical mutagenesis from a field strain isolated from egg breeders in Ningxia, China. It was completely sequenced and its genome annotated; it is presented with the relevant data as a potential vaccine candidate.

A Highly Conserved Peptide Vaccine Candidate Activates Both Humoral and Cellular Immunity Against SARS-CoV-2 Variant Strains

Facing the imminent need for vaccine candidates with cross-protection against globally circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants, we present a conserved antigenic peptide RBD9.1 with both T-cell and B-cell epitopes. RBD9.1 can be recognized by coronavirus disease 2019 (COVID-19) convalescent serum, particularly for those with high neutralizing potency. Immunization with RBD9.1 can successfully induce the production of the receptor-binding domain (RBD)-specific antibodies in Balb/c mice. Importantly, the immunized sera exhibit sustained neutralizing efficacy against multiple dominant SARS-CoV-2 variant strains, including B.1.617.2 that carries a point mutation (SL452R) within the sequence of RBD9.1. Specifically, SY451 and SY454 are identified as the key amino acids for the binding of the induced RBD-specific antibodies to RBD9.1. Furthermore, we have confirmed that the RBD9.1 antigenic peptide can induce a S448-456 (NYNYLYRLF)-specific CD8+ T-cell response. Both RBD9.1-specific B cells and the S448-456-specific T cells can still be activated more than 3 months post the last immunization. This study provides a potential vaccine candidate that can generate long-term protective efficacy over SARS-CoV-2 variants, with the unique functional mechanism of activating both humoral and cellular immunity.

Update on the Inactivation Procedures for the Vaccine Development Prospects of a New Highly Virulent RGNNV Isolate

Viral nervous necrosis (VNN) caused by the nervous necrosis virus (NNV) affects a broad range of primarily marine fish species, with mass mortality rates often seen among larvae and juveniles. Its genetic diversification may hinder the effective implementation of preventive measures such as vaccines. The present study describes different inactivation procedures for developing an inactivated vaccine against a new NNV isolate confirmed to possess deadly effects upon the European seabass (Dicentrarchus labrax), an important Mediterranean farmed fish species that is highly susceptible to this disease. First, an NNV isolate from seabass adults diagnosed with VNN was rescued and the sequences of its two genome segments (RNA1 and RNA2) were classified into the red-spotted grouper NNV (RGNNV) genotype, closely clustering to the highly pathogenic 283.2009 isolate. The testing of different inactivation procedures revealed that the virus particles of this isolate showed a marked resistance to heat (for at least 60 °C for 120 min with and without 1% BSA) but that they were fully inactivated by 3 mJ/cm2 UV-C irradiation and 24 h 0.2% formalin treatment, which stood out as promising NNV-inactivation procedures for potential vaccine candidates. Therefore, these procedures are feasible, effective, and rapid response strategies for VNN control in aquaculture.

Peptides derived from gp43, the most antigenic protein from Paracoccidioides brasiliensis, form amyloid fibrils in vitro: implications for vaccine development

Fungal infection is an important health problem in Latin America, and in Brazil in particular. Paracoccidioides (mainly P. brasiliensis and P. lutzii) is responsible for paracoccidioidomycosis, a disease that affects mainly the lungs. The glycoprotein gp43 is involved in fungi adhesion to epithelial cells, which makes this protein an interesting target of study. A specific stretch of 15 amino acids that spans the region 181–195 (named P10) of gp43 is an important epitope of gp43 that is being envisioned as a vaccine candidate. Here we show that synthetic P10 forms typical amyloid aggregates in solution in very short times, a property that could hamper vaccine development. Seeds obtained by fragmentation of P10 fibrils were able to induce the aggregation of P4, but not P23, two other peptides derived from gp43. In silico analysis revealed several regions within the P10 sequence that can form amyloid with steric zipper architecture. Besides, in-silico proteolysis studies with gp43 revealed that aggregation-prone, P10-like peptides could be generated by several proteases, which suggests that P10 could be formed under physiological conditions. Considering our data in the context of a potential vaccine development, we redesigned the sequence of P10, maintaining the antigenic region (HTLAIR), but drastically reducing its aggregation propensity.