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At least 19 recordsLinked to original sources
PubMed2025

Bacteriophages as vaccine platforms: Opportunities and challenges in translation.

Bacteriophages (phages) have recently received increased interest as versatile candidates for vaccine development. Their inherent characteristics, such as ease of genetic manipulation, high-density antigen display, intrinsic immunostimulatory properties, demonstrated human safety, and scalability in bacterial hosts, make them attractive as next-generation vaccine platforms. Additionally, their cost-effective production, stability, and existing regulatory approval for food and compassionate phage therapy provide a strong foundation for further development of phage-based vaccines. This commentary summarizes the types of phages, the strategies used, and current advances in phage-based vaccine development for viral and bacterial targets, and discusses the promises and challenges of this platform for novel vaccine development. Phage-based vaccines represent an innovative and promising platform for vaccine development to address significant medical and public health challenges, particularly in antimicrobial resistance, pandemic preparedness, and One Health. Accumulative experimental data have demonstrated that phage-based vaccines induce specific cellular, humoral, and mucosal immune responses at magnitudes comparable to those induced by other vaccine platforms. However, a better understanding of phage biology (interactions with the human immune system and microbiome), more carefully designed preclinical studies, Good Manufacturing Practice production development, the regulatory framework, and ultimately clinical trials are needed before the full potential of this platform is realized.

Animals↗
PubMed1978

[Contribution to the treatment of acute haematogenous anc chronic secondary osteomyelitis in children (author's transl)].

The possibility of utilizing antistaphylococcal vaccine and local phage lysate for complex therapy of chronic and acute haematogenous osteomyelitis in children is demonstrated on three clinical cases. The study reassurmes good experience with this therapy in adult patients with chronic osteomyelitis. The results obtained so far in children suggest that the application of antistaphylococcal vaccine and of local phage lysate positively influences the course of the osteomyelitic disease and reduces the number of relpases. In order to specify and intensify the clinical effect of the above mentioned preparations, this method is being employed in other cases of chronic and acute haematogenous osteomyelitis.

Acute Disease↗
PubMed1977

Phage types of Mycobacterium bovis, substrains of BCG.

Nineteen substrains of Mycobacterium bovis, strain bacille Calmette-Guérin (BCG) used in laboratories throughout the world for the preparation of BCG vaccines were phage-typed with a battery of mycobacteriophages. The results revealed differences in their susceptibility to phage lysis that allow subdivision of these strains of BCG into two or more phage types.

BCG Vaccine↗
PubMed2025

A Programmable Nanovaccine Platform Based on M13 Bacteriophage for Personalized Cancer Vaccine and Therapy.

Nanovaccines co-assemble antigens and adjuvants to elicit robust immune responses but often require complex synthesis and post-modification procedures. Here, a programmable nanovaccine platform based on the M13 bacteriophage is developed for the scalable production of vaccines and single-step modular engineering of adjuvanticity, length, and antigen density. By reprogramming the sequence and size of the noncoding phage genome, the Toll-like receptor 9 activation and the length of the phage are precisely controlled. With a novel molecular engineering approach, the antigen density is tuned from 13.6% to 70.3%. A systematic modulation reveals an optimal adjuvanticity at a constant antigen density for maximum anti-tumor CD8+ T cell response, and vice versa, using the model antigen SIINFEKL. The M13 phage-based nanovaccine induces durable memory immunity lasting over a year. In addition, a 24-fold increase in neoantigen-specific CD8+ T cell frequency is achieved when increasing both the adjuvanticity and antigen density. Furthermore, when combined with anti-PD-1 therapy, the M13 phage-based personalized vaccine eradicates established MC-38 tumors in 75% of treated animals and they develop 100% resistance against tumor invasion when challenged 5 months after treatment. These findings establish M13 phage as a powerful and versatile nanovaccine platform with transformative potential for personalized cancer immunotherapy.

Cancer Vaccines↗
PubMedDate not supplied

[Aspects of bacteriophage-eukaryotic cell relationships].

The present work deals with bacteriophage--eukaryotic cell interrelationship, including:--Data on the possible presence of bacteriophages in calf serum and viral vaccines.--Methodological problems of research on phage--eukaryotic cell relations.--Data concerning the effects of phage infection on eukaryotic cells (demonstration of phage infection of the eukaryotic cell; integration of phage genetic material in the genome of the eukaryotic cell; coding of phage proteins in phage-infected eukaryotic cells; modified multiplication parameters and transformed potential of some phage-infected eukaryotic cells).--Indications for solving some of the problems.

Bacteriophages↗
PubMedDate not supplied

[Comparative experimental studies of the combined use of vaccines, interferon and interferon inducers in neurovirus infections].

Comparative investigations of the combined use of vaccines and interferon in tick-borne encephalitis, herpes, and acute encephalomyelitis of man showed that up to 78% of animal protection against 10--50 LD50 of intraperitoneally inoculated viruses could be achieved. Vaccination alone provided up to 56% survival of the infected mice, while administration of interferon subcutaneously or intraperitoneally in a dose of 800 units (53,300 units per 1 kilo body weight) 18--20 hours before virus gave a survival rate of 36%. The use of vaccine in combination with an interferon inducer, phage of f2 RNA, in tick-borne encephalitis gave up to 75% survival of the infected mice. Four hours after administration, interferon could be detected in mouse sera in a concentration up to 640 units/ml which in immune mice accumulated more rapidly and remained at a higher level 18 hours after inoculation of the inducer.

Animals↗
PubMedDate not supplied

Use of polyethyleneglycol-treated serum for animal cell cultures.

Although many proteins will be removed from sera by precipitation with 10% polyethyleneglycol (PEG) the growth-promoting properties of such PEG-treated sera for many cell lines and cell strains are hardly reduced. Among the precipitated proteins are the macroglobulins which are difficult to remove from cell cultures and which may cause allergic reactions if incorporated into vaccines. The gammaglobulins are removed in this way as well. If the sera are contaminated with viruses or phages the titres will be reduced by approximately 4 logs and thus the incidence of virus contamination will be reduced by the PEG-treatment. For foot-and-mouth Disease (FMD) vaccine production PEG-treated sera from vaccinated cattle were applied for cell and virus cultivation. The virus obtained was subsequently precipitated with PEG and collected by filter-aid filtration. A concentrated virus product was obtained, which was practically devoid of serum proteins.

Animals↗
PubMed1979

Artificial Salmonella vaccines: O-antigenic oligosaccharide-protein conjugates induce protection against infection with Salmonella typhimurium.

Outbred mice were vaccinated with various artificial Salmonella vaccines and subsequently challenged intraperitoneally with graded doses of virulent Salmonella typhimurium. The Salmonella vaccines used were: (i) octasaccharide, obtained by hydrolysis of the O-antigenic polysaccharide chain of S. typhimurium strain SH 4809 with phage P22-associated endo-rhamnosidase and covalently linked to either diphtheria toxin or edestine; (ii) purified outer membrane proteins (porins) from S. typhimurium; and (iii) octasaccharide covalently linked to porins. All vaccines induced significant protection against experimental infection of mice with S. typhimurium. However, vaccination with the octasaccharide-porin conjugate resulted in better protection than that obtained by vaccination with octasaccharide or porin vaccines separately. Rabbit antibodies raised against the different vaccines were also passively administered intravenously to mice. Such mice were protected against challenge with virulent S. typhimurium by antibodies specific for the S. typhimurium O-antigen or for the porins. Thus, active immunization with more than one surface component of Salmonella bacteria improved the efficacy of the vaccine. The data from the passive immunization experiments also emphasized the role of humoral immunity for protection against S. typhimurium infection.

Animals↗
PubMed2026

Engineered Bacteriophages in Cancer Immunotherapy: Emerging Concepts and Potential Integration with CAR-T Cell Therapy.

Due to antigen heterogeneity, restricted immune cell trafficking and an immunosuppressive, nutrient-restricted tumour microenvironment, solid tumours remain resistant to modern immunotherapies. Engineered bacteriophages offer a modular framework to overcome these obstacles: programmable virus-like particles with scalable production. Through genome engineering, capsid decoration with mammalian cell-targeting ligands, or hybrid AAV/phage systems, engineered bacteriophages can display tumour-associated antigens, enhance receptor-mediated uptake and deliver therapeutic payloads such as cytokines, chemokines and suicide genes without naturally infecting mammalian cells. These features support their use as vaccine platforms, immunological adjuvants and targeted gene-delivery vehicles. These may enable more precise, tumour-localized therapeutic intervention. Phages can engage innate immune pathways, including TLR9, TLR3/7/8, cGAS-STING and AIM2, promoting dendritic cell maturation and inflammatory mediators that may convert immunologically "cold" tumours into inflamed microenvironments. Their multivalent antigen display enhances B- and T-cell priming, while cDC1-mediated cross-presentation supports cytotoxic CD8+ T-cell responses and immunological memory. In CAR-T therapy, engineered phages may improve tumour homing through chemokine modulation, support persistence through local cytokine delivery, reduce antigen escape by presenting multiple tumour epitopes, and limit T-cell exhaustion through dominant-negative receptor strategies or local checkpoint blockade. This review summarizes engineering approaches, delivery systems, manufacturing, biodistribution, dosing, and safety issues, including immunogenicity, pre-existing anti-phage antibodies and horizontal gene transfer. It also distinguishes therapeutic engineered phage particles from phage display technologies used for molecular discovery. Despite encouraging results integrating modified bacteriophages with CAR-T cell therapy, the evidence remains mostly preclinical, indicating both substantial translational prospects and crucial obstacles for future clinical development.

CAR-T cell therapy↗
PubMed1977

Bacteriophages in live virus vaccines: lack of evidence for effects on the genome of rhesus monkeys.

Four juvenile rhesus monkeys were inoculated with 10(12) plaque-forming units of the bacteriophage phiV1 isolated from live virus vaccines. After phiV1 had been cleared from the blood, DNA's were isolated from the livers and kidneys and analyzed for the presence of bacteriophage by plaque assays, and for the presence of phiV1 DNA by DNA-DNA reassociation kinetics. No evidence was found for persistence of the bacteriophage or for replication of the phage genome in these rhesus monkeys.

Animals↗
PubMed1977

Staphylococcal infections.

All the forms of staphylococcal infections require cooperation among microbiologists, immunologists and clinicians. In case of any acute staphylococcus process, the curative tactics is based on an effective chemotherapy sometimes completed by a radical surgical intervention. In case of chronic forms, however, the antibiotics therapy is considered to be problematic. It is the specific immunotherapy by means of specific vaccine with polyvalent action, containing all pathogenetically significant antigens, that is considered by the authors to be a reliable base of the therapy of chronic staphylococcus infections. The specific polyvalent phage lysate is used for local application. It has to be pointed out that this therapy requires a complex curative regimen, i.e. regulation of the deficiency of serum immunoglobulines, administration of antibiotics, amelioration of the tissue trophism of the area concerned, suitable therapy by means of vitamines and diet. If necessary, surgical technique and tactics are an important part of the entire complex curative method.

Chronic Disease↗
PubMed1975

[Clinical study of the efficacy of staphylococcal anatoxin in relation to the phage group to which the staphylococcal strains--the causative agents of infection--belong].

In comparing the bacteriophage group reference of the strains of pathogenic staphylococci isolated in case of postoperative complications from children given staphylococcus toxoid for prophylactic purpose and from control group it was found that prophylactic vaccinations of staphylococcus toxoid created the most intense immunity against staphylococci of the I bacteriophage group. There was found no significant association between the efficacy of the therapy and bacteriophage reference of staphylococci--the causative agents of the infection.

Bacteriophage Typing↗
PubMed1977

[Detection of the localization of C1. botulinum antigens in regional lymph node cells by the immunofluorescence technic].

As a result of the study of lacalization of the C1. botulinum toxoids of the A, B, and E types in cells of the regional lymph nodes of rabbits by the indirect Coons' method and by the smear-print method it was revealed that different types of lymphoid tissue cells took part in the ingestion and digestion of these antigens; the antigens of the A and B types were at first revealed in the cytoplasm of pseudoeosinophils, and then in the macrophages. The antigen of the E type was revealed in the course of the whole experiment in the macro phages of the regional lymph node, although the number of pseudoeosinophils also increased. Apparently there was a different activity of pseudoeosinophils against the C1. botulinum toxoids, the types A, B and E.

Animals↗
PubMed2025

Evolution of antibody cross-reactivity to influenza H5N1 neuraminidase from an N2-specific germline.

The ongoing spread of highly pathogenic avian influenza H5N1 clade 2.3.4.4b virus in animals and its occasional spillover to humans have raised concerns about a potential H5N1 pandemic. Although recent studies have shown that pre-existing human antibodies can recognize H5N1 neuraminidase, the molecular basis of how this cross-reactivity develops remains poorly understood. In this study, we used a phage display antibody library derived from 245 healthy donors to isolate an antibody, HB420, that cross-reacts with neuraminidases of human H3N2 and avian H5N1 clade 2.3.4.4b viruses and confers protection in vivo. Cryogenic electron microscopy analysis reveals that HB420 targets the neuraminidase active site by mimicking sialic acid binding through a single Asp residue. Furthermore, the inferred germline of HB420 is N2 specific but acquires cross-reactivity to H5N1 neuraminidase through somatic hypermutation. Overall, our findings provide insights into how neuraminidase antibody evolves breadth, which has important implications for the development of broadly protective influenza vaccines.

Influenza A Virus, H5N1 Subtype↗