Advances in Vaccines and Antimicrobial Therapy

Topic Information

Dear Colleagues,

The fields of prevention and treatment of infectious diseases have been gaining momentum after the strike of the coronavirus pandemic, with several advances both in vaccine technology and in the development of new antimicrobials. The usefulness of monoclonal antibodies has been tested, along with several old and new compounds with antiviral activity, but the search for new avenues, combining diverse strategies and reexamining older drugs for potential new activities, is quickly evolving. Interactions of drugs with the local microbiota, combinations of systemic approaches, targeting immune defense mechanisms together with arresting microbial host invasion, refinements in nano-formulations, drug delivery, rapid genotyping of microorganisms and engineering of bacteriophages in the fight against multidrug resistance are just some of the areas in which breakthrough research is expected to bring significant advances in the near future. The aim of this Topic is to offer an updated view of the advances in all the fields of antimicrobial therapy and prevention. This Topic collection invites contributions of research articles, reviews and metanalyses, exploring the new horizons of antimicrobial therapy and vaccine development. Both in vitro and in vivo studies, field studies and reports, as well as bold new hypotheses based on original observations are also welcome. We as Editors expect both academic research institutions and industry research to be represented in this collection on issues of primary relevance for health systems and individual safety in the near future.

Dr. Roberto Paganelli
Dr. Raffaele D’Amelio
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Antibiotics antibiotics	4.3	7.3	2012	15.8 Days	CHF 2900
Biomedicines biomedicines	3.9	5.2	2013	14.6 Days	CHF 2600
Microorganisms microorganisms	4.1	7.4	2013	11.7 Days	CHF 2700
Parasitologia parasitologia	-	1.7	2021	19.2 Days	CHF 1000
Pathogens pathogens	3.3	6.4	2012	15.3 Days	CHF 2200
Vaccines vaccines	5.2	8.9	2013	18.6 Days	CHF 2700

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Published Papers (21 papers)

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All Antibiotics Biomedicines Microorganisms Parasitologia Pathogens Vaccines

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18 pages, 6369 KiB  

Open AccessReview

Progress on Respiratory Syncytial Virus Vaccine Development and Evaluation Methods

by Lie Deng, Hongjie Cao, Guichang Li, Kaiwen Zhou, Zihan Fu, Jiaying Zhong, Zhongfang Wang and Xiaoyun Yang

Vaccines 2025, 13(3), 304; https://doi.org/10.3390/vaccines13030304 - 12 Mar 2025

Cited by 1 | Viewed by 1375

Abstract

Respiratory syncytial virus (RSV) remains a significant global health threat, especially to infants, the elderly, and immunocompromised individuals. This review comprehensively explores the progress in RSV vaccine development, the immune evaluation methods, and immunological surrogate. The RSV fusion (F) protein, a primary target [...] Read more.

Respiratory syncytial virus (RSV) remains a significant global health threat, especially to infants, the elderly, and immunocompromised individuals. This review comprehensively explores the progress in RSV vaccine development, the immune evaluation methods, and immunological surrogate. The RSV fusion (F) protein, a primary target for vaccine development, has been engineered in prefusion conformation to elicit potent neutralizing antibodies, while the attachment (G) glycoprotein and other immunogens are also being explored to broaden immune responses. Advances in diverse vaccine platforms, ranging from live attenuated and protein subunit vaccines to cutting-edge mRNA- and nanoparticle-based formulations, highlight the field’s progress, yet challenges in balancing safety, immunogenicity, and durability persist. Central to these efforts is the identification and validation of immunological surrogates, which may serve as critical benchmarks for vaccine efficacy. Neutralizing antibody titers, multifunctional T cell responses, and B cell memory have emerged as key correlates of protection. However, the feasibility of these surrogates depends on their ability to predict clinical outcomes across diverse populations and settings. While neutralizing antibodies block the virus directly, T cell responses are essential for clearing infected cells and preventing severe disease, and B cell memory ensures long-term immunity. Integrating these immunological markers into a cohesive framework requires standardized assays, robust clinical validation, and an in-depth understanding of RSV-induced immune response. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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19 pages, 3723 KiB  

Open AccessArticle

Genome Sequencing and Assembly of Enterotoxigenic Escherichia coli E9034A: Role of LngA, CstH, and FliC in Intestinal Cell Colonization and the Release of the Proinflammatory Cytokine IL-8

by Ricardo Rodríguez-Martínez, Sara A. Ochoa, Ricardo Valle-Rios, Gustavo A. Jaimes-Ortega, Rigoberto Hernández-Castro, Jetsi Mancilla-Rojano, Graciela Castro-Escarpulli, Catalina López-Saucedo, Teresa Estrada-García, Ariadnna Cruz-Córdova and Juan Xicohtencatl-Cortes

Microorganisms 2025, 13(2), 374; https://doi.org/10.3390/microorganisms13020374 - 8 Feb 2025

Viewed by 808

Abstract

Enterotoxigenic Escherichia coli (ETEC) produces two types of enterotoxins, LTs and STs, as well as several colonization factors (CFs), including CS21, CS3 fimbriae, and flagellar structures. This study investigated how these structures contribute to ETEC colonization and the immune response in HT-29 and [...] Read more.

Enterotoxigenic Escherichia coli (ETEC) produces two types of enterotoxins, LTs and STs, as well as several colonization factors (CFs), including CS21, CS3 fimbriae, and flagellar structures. This study investigated how these structures contribute to ETEC colonization and the immune response in HT-29 and HuTu-80 intestinal cells. ETEC strains with single, double, and triple mutations in the lngA, cstH, and fliC genes were generated and confirmed using PCR and Western blotting. The colonization of HT-29 and HuTu-80 intestinal cells by the ETEC E9034A strain, which was fully sequenced using a hybrid approach involving both Illumina and Oxford Nanopore technologies, was used to generate the mutant and recombinant proteins. The colonization and adherence of E9034A and its mutants were assessed through colony-forming unit (CFU) counts. Cytokine levels were assessed using flow cytometry and analyzed via FlowJo 7.6.1. Quantitative analysis revealed that the absence of the lngA, cstH, and fliC genes significantly (p < 0.01) reduced ETEC adherence to HT-29 and HutU-80 cells. In addition, only ETEC strains expressing the FliC protein induced IL-8 secretion. These findings suggest that LngA, CstH, and FliC in ETEC E9034A enhance adherence to intestinal cells and trigger the release of IL-8. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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13 pages, 2269 KiB  

Open AccessArticle

Characterization and Protective Efficacy of a Salmonella Typhimurium ATCC 14028 sptP Mutant as a Live Attenuated Vaccine Candidate

by Nanlong Zhou, Yonghui Ding, Ting He, Yuling Sun, Hongfang Chen, Meiling Huang and Tiansen Li

Vaccines 2025, 13(2), 150; https://doi.org/10.3390/vaccines13020150 - 31 Jan 2025

Viewed by 962

Abstract

Background: Salmonella Typhimurium poses a substantial health risk to both humans and animals. This study evaluated the potential of using the Salmonella Typhimurium ΔsptP mutant as a live-attenuated vaccine candidate by constructing it through homologous recombination and assessing its key biological properties, including growth [...] Read more.

Background: Salmonella Typhimurium poses a substantial health risk to both humans and animals. This study evaluated the potential of using the Salmonella Typhimurium ΔsptP mutant as a live-attenuated vaccine candidate by constructing it through homologous recombination and assessing its key biological properties, including growth characteristics, immunogenicity, and protective efficacy. Methods: We generated the ΔsptP mutant through targeted gene deletion, ensuring the preservation of the bacterial strain’s growth and stability. In vitro and in vivo assays were performed to compare the invasive capabilities between the mutant and the wild-type strains. Specifically, we examined the invasion into RAW264.7 murine macrophages and mice. Furthermore, the virulence of the mutant was evaluated by determining the median lethal dose (LD₅₀). To evaluate immunogenicity and protection, mice were immunized with 2 × 10⁴ CFUs of the ΔsptP mutant, followed by a booster immunization, and then challenged with a virulent strain. Results: The ΔsptP mutant exhibited no significant changes in growth characteristics or genetic stability compared to the wild-type strain. However, it demonstrated a significantly diminished capacity for invasion in both murine macrophages and mice. The LD₅₀ for the mutant was 39.92-fold higher than that of the wild-type, indicating a marked reduction in virulence. Mice immunized with the ΔsptP mutant and administered a booster immunization exhibited 87.5% protection against challenge with a virulent strain, as compared to the PBS control group. Moreover, the mutant induced IgG antibody levels comparable to those induced by the wild-type strain. Conclusions: The ΔsptP mutant of Salmonella Typhimurium exhibits markedly reduced virulence while retaining robust immunogenicity and protective efficacy. These findings suggest that the ΔsptP mutant is a promising candidate for a live-attenuated vaccine, potentially providing an effective strategy to prevent Salmonella Typhimurium infections. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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43 pages, 1654 KiB  

Open AccessReview

mRNA Vaccines Against COVID-19 as Trailblazers for Other Human Infectious Diseases

by Rossella Brandi, Alessia Paganelli, Raffaele D’Amelio, Paolo Giuliani, Florigio Lista, Simonetta Salemi and Roberto Paganelli

Vaccines 2024, 12(12), 1418; https://doi.org/10.3390/vaccines12121418 - 16 Dec 2024

Cited by 1 | Viewed by 2771

Abstract

mRNA vaccines represent a milestone in the history of vaccinology, because they are safe, very effective, quick and cost-effective to produce, easy to adapt should the antigen vary, and able to induce humoral and cellular immunity. Methods: To date, only two COVID-19 mRNA [...] Read more.

mRNA vaccines represent a milestone in the history of vaccinology, because they are safe, very effective, quick and cost-effective to produce, easy to adapt should the antigen vary, and able to induce humoral and cellular immunity. Methods: To date, only two COVID-19 mRNA and one RSV vaccines have been approved. However, several mRNA vaccines are currently under development for the prevention of human viral (influenza, human immunodeficiency virus [HIV], Epstein–Barr virus, cytomegalovirus, Zika, respiratory syncytial virus, metapneumovirus/parainfluenza 3, Chikungunya, Nipah, rabies, varicella zoster virus, and herpes simplex virus 1 and 2), bacterial (tuberculosis), and parasitic (malaria) diseases. Results: RNA viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV)-2, HIV, and influenza, are characterized by high variability, thus creating the need to rapidly adapt the vaccines to the circulating viral strain, a task that mRNA vaccines can easily accomplish; however, the speed of variability may be higher than the time needed for a vaccine to be adapted. mRNA vaccines, using lipid nanoparticles as the delivery system, may act as adjuvants, thus powerfully stimulating innate as well as adaptive immunity, both humoral, which is rapidly waning, and cell-mediated, which is highly persistent. Safety profiles were satisfactory, considering that only a slight increase in prognostically favorable anaphylactic reactions in young females and myopericarditis in young males has been observed. Conclusions: The COVID-19 pandemic determined a shift in the use of RNA: after having been used in medicine as micro-RNAs and tumor vaccines, the new era of anti-infectious mRNA vaccines has begun, which is currently in great development, to either improve already available, but unsatisfactory, vaccines or develop protective vaccines against infectious agents for which no preventative tools have been realized yet. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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14 pages, 6300 KiB  

Open AccessArticle

H9 Consensus Hemagglutinin Subunit Vaccine with Adjuvants Induces Robust Mucosal and Systemic Immune Responses in Mice by Intranasal Administration

by Liming Lin, Shunfan Zhu, Beibei Yang, Xin Zhang, Huimin Wu, Shixiang Wu, Li Wu, Jianhong Shu, Yulong He and Huapeng Feng

Microorganisms 2024, 12(11), 2294; https://doi.org/10.3390/microorganisms12112294 - 12 Nov 2024

Viewed by 1260

Abstract

The H9N2 subtype avian influenza viruses mainly cause respiratory symptoms, reduce the egg production and fertility of poultry, and result in secondary infections, posing a great threat to the poultry industry and human health. Currently, all H9N2 avian influenza commercial vaccines are inactivated [...] Read more.

The H9N2 subtype avian influenza viruses mainly cause respiratory symptoms, reduce the egg production and fertility of poultry, and result in secondary infections, posing a great threat to the poultry industry and human health. Currently, all H9N2 avian influenza commercial vaccines are inactivated vaccines, which provide protection for immunized animals but cannot inhibit the spread of the virus and make it difficult to distinguish between the infected animals and vaccinated animals. In this study, a trimeric consensus H9 hemagglutinin (HA) subunit vaccine for the H9N2 subtype avian influenza virus based on a baculovirus expression system was first generated, and then the effects of three molecular adjuvants on the H9 HA subunit vaccine, Cholera toxin subunit B (CTB), flagellin, and granulocyte-macrophage colony-stimulating factor (GM-CSF) fused with H9 HA, and one synthetic compound, a polyinosinic–polycytidylic acid (PolyI:C) adjuvant, were evaluated in mice by intranasal administration. The results showed that these four adjuvants enhanced the immunogenicity of the H9 HA subunit vaccine for avian influenza viruses, and that GM-CSF and PolyI:C present better mucosal adjuvant activity for the H9 HA subunit vaccine. These results demonstrate that we have developed a potential universal H9 HA mucosal subunit vaccine with adjuvants in a baculovirus system that would be helpful for the prevention and control of H9N2 subtype avian influenza viruses. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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14 pages, 11775 KiB  

Open AccessArticle

Development of a Novel Chimeric ND-GP cVLPs Vaccine for the Prevention of Goose-Derived Newcastle Disease and Gosling Plague

by Jindou Li, Jiaxin Ding, Chunhong Guo, Xiaohong Xu, Chunhui Shan, Jing Qian and Zhuang Ding

Microorganisms 2024, 12(11), 2266; https://doi.org/10.3390/microorganisms12112266 - 8 Nov 2024

Cited by 1 | Viewed by 1154

Abstract

Goose-derived Newcastle disease (ND) and gosling plague (GP) are serious threats to the goose industry. Conventional vaccines have made significant contributions to preventing GP and ND. Nevertheless, the renewal of conventional vaccines and the application of novel vaccines are urgently needed to align [...] Read more.

Goose-derived Newcastle disease (ND) and gosling plague (GP) are serious threats to the goose industry. Conventional vaccines have made significant contributions to preventing GP and ND. Nevertheless, the renewal of conventional vaccines and the application of novel vaccines are urgently needed to align with eco-friendly and efficient breeding concepts and achieve the final goal of epidemic purification. Therefore, based on the Newcastle disease virus-like particles (ND VLPs) vector platform, we developed novel chimeric ND-GP bivalent cVLPs (ND-GP cVLPs) displaying the NDV HN protein and the GPV VP3 protein. In vivo, immunization experiments revealed that geese immunized with 30 µg, 50 µg, or 70 µg of the ND-GP cVLPs and commercial vaccines produced highly effective hemagglutination inhibitory antibodies against NDV and neutralizing antibodies against GPV, respectively. Furthermore, 70 µg of the ND-GP cVLPs effectively protected against virulent NDV and GPV, reducing tissue damage from viral infection and virus shedding in the oropharynx and cloaca. In conclusion, we provide eco-friendly and efficient novel ND-GP cVLPs for preventing goose-derived ND and GP. Our findings provide the basis for using ND VLPs as foreign protein carriers for the developing of multi-conjugate vaccines. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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28 pages, 4936 KiB  

Open AccessArticle

An Immunoinformatic Approach for Identifying and Designing Conserved Multi-Epitope Vaccines for Coronaviruses

by Yu Chuan Ong, Bimo Ario Tejo and Wei Boon Yap

Biomedicines 2024, 12(11), 2530; https://doi.org/10.3390/biomedicines12112530 - 5 Nov 2024

Viewed by 1391

Abstract

Background/Objectives: The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has exposed the vulnerabilities and unpreparedness of the global healthcare system in dealing with emerging zoonoses. In the past two decades, coronaviruses (CoV) have been responsible for [...] Read more.

Background/Objectives: The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has exposed the vulnerabilities and unpreparedness of the global healthcare system in dealing with emerging zoonoses. In the past two decades, coronaviruses (CoV) have been responsible for three major viral outbreaks, and the likelihood of future outbreaks caused by these viruses is high and nearly inevitable. Therefore, effective prophylactic universal vaccines targeting multiple circulating and emerging coronavirus strains are warranted. Methods: This study utilized an immunoinformatic approach to identify evolutionarily conserved CD4+ (HTL) and CD8+ (CTL) T cells, and B-cell epitopes in the coronaviral spike (S) glycoprotein. Results: A total of 132 epitopes were identified, with the majority of them found to be conserved across the bat CoVs, pangolin CoVs, endemic coronaviruses, SARS-CoV-2, and Middle East respiratory syndrome coronavirus (MERS-CoV). Their peptide sequences were then aligned and assembled to identify the overlapping regions. Eventually, two major peptide assemblies were derived based on their promising immune-stimulating properties. Conclusions: In this light, they can serve as lead candidates for universal coronavirus vaccine development, particularly in the search for pan-coronavirus multi-epitope universal vaccines that can confer protection against current and novel coronaviruses. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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12 pages, 1600 KiB  

Open AccessArticle

Immunometabolic Regulation of Vaccine-Induced Antibody Responses in Aging Mice

by Daniela Frasca, Maria Romero, Laura Padula, Eva Fisher and Natasa Strbo

Vaccines 2024, 12(9), 960; https://doi.org/10.3390/vaccines12090960 - 26 Aug 2024

Cited by 1 | Viewed by 1399

Abstract

Immune cells undergo metabolic reprogramming to meet the demands associated with immune responses. The effects of aging on these pathways and on the metabolic phenotype of the immune cells participating in antibody responses to vaccines are still largely unknown. Here we used a [...] Read more.

Immune cells undergo metabolic reprogramming to meet the demands associated with immune responses. The effects of aging on these pathways and on the metabolic phenotype of the immune cells participating in antibody responses to vaccines are still largely unknown. Here we used a vaccine for SARS-CoV-2 that utilizes the cellular heat shock chaperone glycoprotein 96 (gp96), engineered to co-express SARS-CoV-2 Spike (spike) protein (gp96-Ig-S). Results show that this vaccine induces comparable B cell primary responses in young and old mice at later time points, but a significantly lesser secondary response in old as compared to young mice, with the antibodies generated in the secondary response being also of lower avidity. This occurs because aging changes the B cell metabolic phenotype and induces hyper-metabolic B cells that are associated with higher intrinsic inflammation and decreased protective antibody responses. However, the gp96-Ig-S vaccine was found to be effective in significantly reducing the metabolic/inflammatory status of B cells from old mice, suggesting the possibility that targeting metabolic pathways may improve immune function in old mice that do not respond adequately to the vaccine. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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16 pages, 4186 KiB  

Open AccessArticle

Immunogenicity and Cross-Protection Efficacy of a Genotype F-Derived Attenuated Virus Vaccine Candidate against Mumps Virus in Mice

by Seo-Yeon Kim, Hyeran Won, Yun-Ho Hwang, Se-Eun Kim, Jung-Ah Lee, Dokeun Kim, You-Jin Kim and Tae-Young Lee

Vaccines 2024, 12(6), 595; https://doi.org/10.3390/vaccines12060595 - 30 May 2024

Viewed by 1315

Abstract

Mumps virus (MuV) causes an acute contagious human disease characterized by swelling of the parotid glands. Despite the near elimination of mumps in many countries, the disease has recurred, even in vaccinated populations, especially adolescents. Immunization effectivity of the genotype A vaccine strain [...] Read more.

Mumps virus (MuV) causes an acute contagious human disease characterized by swelling of the parotid glands. Despite the near elimination of mumps in many countries, the disease has recurred, even in vaccinated populations, especially adolescents. Immunization effectivity of the genotype A vaccine strain Jeryl Lynn (JL) is declining as genotype A is no longer predominant; therefore, a new vaccine strain and booster vaccine are required. We generated a cell culture-adapted MuV genotype F called F30 and evaluated its immunogenicity and cross-protective activity against diverse genotypes. F30 genome nucleotide sequence determination revealed changes in the NP, L, SH, and HN genes, leading to five amino acid changes compared to a minimally passaged stock (F10). F30 showed delayed growth, smaller plaque size in Vero cells, and lower neurotoxicity in neonatal mice than F10. Furthermore, F30 was immunogenic to other genotypes, including the JL vaccine strain, with higher efficacy than that of JL for homologous and heterologous immunization. Further, F30 exhibited cross-protective immunity against MuV genotypes F and G in Ifnar^−/− mice after a third immunization with F30 following two doses of JL. Our data suggest that the live-attenuated virus F30 could be an effective booster vaccine to control breakthrough infections and mumps epidemics. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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15 pages, 3801 KiB  

Open AccessArticle

An Adjuvanted Vaccine-Induced Pathogenesis Following Influenza Virus Infection

by Shiou-Chih Hsu, Kun-Hsien Lin, Yung-Chieh Tseng, Yang-Yu Cheng, Hsiu-Hua Ma, Ying-Chun Chen, Jia-Tsrong Jan, Chung-Yi Wu and Che Ma

Vaccines 2024, 12(6), 569; https://doi.org/10.3390/vaccines12060569 - 23 May 2024

Viewed by 1591

Abstract

An incomplete Freund’s adjuvant elicited an overt pathogenesis in vaccinated mice following the intranasal challenge of A/California/07/2009 (H1N1) virus despite the induction of a higher specific antibody titer than other adjuvanted formulations. Aluminum hydroxide adjuvants have not induced any pathogenic signs in a [...] Read more.

An incomplete Freund’s adjuvant elicited an overt pathogenesis in vaccinated mice following the intranasal challenge of A/California/07/2009 (H1N1) virus despite the induction of a higher specific antibody titer than other adjuvanted formulations. Aluminum hydroxide adjuvants have not induced any pathogenic signs in a variety of formulations with glycolipids. A glycolipid, α-galactosyl ceramide, improved a stimulatory effect of distinct adjuvanted formulations on an anti-influenza A antibody response. In contrast to α-galactosyl ceramide, its synthetic analogue C34 was antagonistic toward a stimulatory effect of an aluminum hydroxide adjuvant on a specific antibody response. The aluminum hydroxide adjuvant alone could confer complete vaccine-induced protection against mortality as well as morbidity caused by a lethal challenge of the same strain of an influenza A virus. The research results indicated that adjuvants could reshape immune responses either to improve vaccine-induced immunity or to provoke an unexpected pathogenic consequence. On the basis of these observations, this research connotes the prominence to develop a precision adjuvant for innocuous vaccination aimed at generating a protective immunity without aberrant responses. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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22 pages, 2127 KiB  

Open AccessArticle

Design of a New Vaccine Prototype against Porcine Circovirus Type 2 (PCV2), M. hyopneumoniae and M. hyorhinis Based on Multiple Antigens Microencapsulation with Sulfated Chitosan

by Darwuin Arrieta-Mendoza, Bruno Garces, Alejandro A. Hidalgo, Victor Neira, Galia Ramirez, Andrónico Neira-Carrillo and Sergio A. Bucarey

Vaccines 2024, 12(5), 550; https://doi.org/10.3390/vaccines12050550 - 17 May 2024

Viewed by 1952

Abstract

This work evaluated in vivo an experimental-multivalent-vaccine (EMV) based on three Porcine Respiratory Complex (PRC)-associated antigens: Porcine Circovirus Type 2 (PCV2), M. hyopneumoniae (Mhyop) and M. hyorhinis (Mhyor), microencapsulated with sulfated chitosan (M- ChS + PRC-antigens), postulating chitosan sulphate (ChS) as a mimetic [...] Read more.

This work evaluated in vivo an experimental-multivalent-vaccine (EMV) based on three Porcine Respiratory Complex (PRC)-associated antigens: Porcine Circovirus Type 2 (PCV2), M. hyopneumoniae (Mhyop) and M. hyorhinis (Mhyor), microencapsulated with sulfated chitosan (M- ChS + PRC-antigens), postulating chitosan sulphate (ChS) as a mimetic of the heparan sulfate receptor used by these pathogens for cell invasion. The EMV was evaluated physicochemically by SEM (Scanning-Electron-Microscopy), EDS (Energy-Dispersive-Spectroscopy), Pdi (Polydispersity-Index) and zeta potential. Twenty weaned pigs, distributed in four groups, were evaluated for 12 weeks. The groups 1 through 4 were as follows: 1-EMV intramuscular-route (IM), 2-EMV oral-nasal-route (O/N), 3-Placebo O/N (M-ChS without antigens), 4-Commercial-vaccine PCV2-Mhyop. qPCR was used to evaluate viral/bacterial load from serum, nasal and bronchial swab and from inguinal lymphoid samples. Specific humoral immunity was evaluated by ELISA. M-ChS + PRC-antigens measured between 1.3–10 μm and presented low Pdi and negative zeta potential, probably due to S (4.26%). Importantly, the 1-EMV protected 90% of challenged animals against PCV2 and Mhyop and 100% against Mhyor. A significant increase in antibody was observed for Mhyor (1-EMV and 2-EMV) and Mhyop (2-EMV), compared with 4-Commercial-vaccine. No difference in antibody levels between 1-EMV and 4-Commercial-vaccine for PCV2-Mhyop was observed. Conclusion: The results demonstrated the effectiveness of the first EMV with M-ChS + PRC-antigens in pigs, which were challenged with Mhyor, PCV2 and Mhyop, evidencing high protection for Mhyor, which has no commercial vaccine available. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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13 pages, 936 KiB  

Open AccessArticle

Activity of Epsilon-poly-L-lysine against Multidrug-Resistant Pseudomonas aeruginosa and Klebsiella pneumoniae Isolates of Urinary Tract Infections

by Telma de Sousa, Carolina Sabença, Miguel Ribeiro, Mario Pino-Hurtado, Carmen Torres, Michel Hébraud, Olimpia Alves, Sara Sousa, Eliana Costa, Gilberto Igrejas and Patrícia Poeta

Biomedicines 2024, 12(3), 638; https://doi.org/10.3390/biomedicines12030638 - 13 Mar 2024

Viewed by 2586

Abstract

Pseudomonas aeruginosa and Klebsiella pneumoniae are notorious for their resistance to antibiotics and propensity for biofilm formation, posing significant threats to human health. Epsilon-poly-L-lysine (ε-PL) emerges as a naturally occurring antimicrobial poly(amino acid), which positions it as a prospective agent for addressing challenges [...] Read more.

Pseudomonas aeruginosa and Klebsiella pneumoniae are notorious for their resistance to antibiotics and propensity for biofilm formation, posing significant threats to human health. Epsilon-poly-L-lysine (ε-PL) emerges as a naturally occurring antimicrobial poly(amino acid), which positions it as a prospective agent for addressing challenges linked to multidrug resistance. ε-PL symbolizes a promising avenue in the pursuit of efficacious therapeutic strategies and warrants earnest consideration within the realm of clinical treatment. Thus, our objective was to determine the antibiotic susceptibility profiles of 38 selected P. aeruginosa and ESBL-producing K. pneumoniae clinical isolates and determine the ability of ε-PL to inhibit biofilm formation. After PCR analysis, detection of genes related to β-lactamases was observed among the selected isolates of P. aeruginosa [bla_SPM (35.7%), bla_KPC (35.7%), bla_SHV (14.3%), bla_CTX-M (14.3%), bla_OXA (14.3%), bla_TEM (7.1%), bla_PER (7.1%), bla_VIM (7.1%), and bla_VIM-2 (7.1%)] and K. pneumoniae [bla_CTX-M (91.7%), bla_TEM (83.3%), bla_KPC (16.7%), bla_NDM (12.5%), and bla_OXA (4.2%)]. The results of testing the activity of ε-PL against the clinical isolates showed relatively high minimum inhibitory concentrations (MICs) for the P. aeruginosa (range: 8–64 µg/mL) and K. pneumoniae isolates (range: 16–32 µg/mL). These results suggest the need for prior optimization of ε-PL concerning its viability as an alternative to antibiotics for treating infections caused by P. aeruginosa and K. pneumoniae of clinical origin. It is noteworthy that, in the context of a low antibiotic discovery rate, ε-PL could play a significant role in this quest, considering its low toxicity and the unlikely development of resistance. Upon exposure to ε-PL, P. aeruginosa and K. pneumoniae isolates exhibited a reduction in biofilm production, with ε-PL concentration showing an inverse relationship, particularly in isolates initially characterized as strong or moderate producers, indicating its potential as a natural antimicrobial agent with further research needed to elucidate optimal concentrations and application methods across different bacterial species. Further research is needed to optimize its use and explore its potential in various applications. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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11 pages, 3020 KiB  

Open AccessArticle

The Stability and Efficency of CPB Cells Were Acclimated for Virus Proliferation

by Yinjie Niu, Saiya Ma, Hongru Liang, Xiaozhe Fu, Baofu Ma, Qiang Lin, Xia Luo and Ningqiu Li

Vaccines 2024, 12(3), 220; https://doi.org/10.3390/vaccines12030220 - 20 Feb 2024

Viewed by 1485

Abstract

Background: Vaccinations are still the most effective means of preventing and controlling fish viral diseases, and cells are an important substrate for the production of a viral vaccine. Therefore, the rapid-stable growth and virus sensitivity of cells are urgently needed. Methods: Chinese perch [...] Read more.

Background: Vaccinations are still the most effective means of preventing and controlling fish viral diseases, and cells are an important substrate for the production of a viral vaccine. Therefore, the rapid-stable growth and virus sensitivity of cells are urgently needed. Methods: Chinese perch brain 100th passage (CPB p100) were acclimated in a low serum with 5% FBS L-15 for 50 passages, then transferred to 8% FBS L-15 for 150 passages. Additionally, the morphology and cell type of CPB 300th passage (CPB p300) cells were identified. We analyzed the transfection efficiency and virus sensitivity of CPB p300 cells, and then optimized the conditions of ISKNV, SCRV, and LMBV multiplication in CPB cells. Results: CPB p300 cells were more homogeneous, and the spread diameter (20–30) µm in CPB p300 cells became the dominant population. The doubling time of CPB p300 was 1.5 times shorter than that of CPB p100.However, multiplication rate of CPB p300 was 1.37 times higher than CPB p100. CPB p300 cells were susceptible to ISKNV, SCRV, and LMBV, and the optimal conditions of ISKNV, SCRV, and LMBV multiplication were simultaneous incubation, 0.6 × 10⁵ cells/cm² and MOI = 0.1; infection at 48 h, 0.8 × 10⁵ cells/cm² and MOI = 0.01; simultaneous incubation, 0.7 × 10⁵ cells/cm² and MOI = 0.05, respectively. The time and economic costs of ISKNV, SCRV, and LMBV multiplication in CPB p300 cells were significantly reduced. Conclusions: The acquisition of CPB p300 cells laid a good material foundation for the production of ISKNV, SCRV, and LMBV vaccines. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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13 pages, 1092 KiB  

Open AccessArticle

Quantitative Analysis of the Instant and Persistent Inhibition Effects of Maternal Poliovirus Antibodies on the Immune Response in a Phase IV Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine

by Qiongzhou Yin, Yan Zheng, Zhifang Ying, Jingyu Li, Ya Jiang, Wenmei Bao, Youjian Dou, Yi Pu, Jin Lei, Haitao Yang, Ruiju Jiang, Yan Deng, Zhimei Zhao, Jing Pu, Jing Yang, Yadong Li, Min Xu, Wei Cai, Yanchun Che and Li Shi

Vaccines 2024, 12(2), 217; https://doi.org/10.3390/vaccines12020217 - 19 Feb 2024

Viewed by 1880

Abstract

Background: An inactivated poliomyelitis vaccine made from Sabin strains (sIPVs) has widely been used in China since 2015. However, the quantitative data on the instant and persistent inhibition effects of maternal poliovirus antibodies on the immune response to sIPV priming and booster vaccination [...] Read more.

Background: An inactivated poliomyelitis vaccine made from Sabin strains (sIPVs) has widely been used in China since 2015. However, the quantitative data on the instant and persistent inhibition effects of maternal poliovirus antibodies on the immune response to sIPV priming and booster vaccination have not been available yet. Objective: In this study, we aim to explore and quantify the instant and persistent inhibition effect of maternal poliovirus antibodies on the immune response elicited by sIPV primary and booster vaccination. Methods: The immunogenicity data consisting of the days 0 and 30 after the prime and booster vaccination of the sIPV in a phase IV trial were pooled for a quantitative analysis of the inhibition effect of maternal poliovirus antibody. The geometric mean ratio (GMR) was calculated using linear regression models, representing that every 2-fold higher maternal poliovirus antibody titer may result in a (1-GMR) lower postimmunization antibody titer. Results: The GMRs for poliovirus types 1, 2, and 3 were 0.79 (0.77–0.82), 0.85 (0.81–0.89), and 0.87 (0.83–0.91) at 30 days after the priming series, 0.86 (0.83–0.89), 0.81 (0.76–0.85), and 0.86 (0.80–0.93) at one year after the priming series, and 0.96 (0.94–0.99), 0.89 (0.86–0.93), and 0.98 (0.93–1.03) at 30 days after the booster dose. The inhibition effect continued to exist until the booster dose 1 year later, and such a persistent inhibition effect was almost attenuated for poliovirus types 1 and 3, and partly reduced for type 2 at 30 days after the booster dose. Conclusion: A wider interval between the four sIPV doses might be a consideration for reducing the effect of maternal antibodies and subsequently eliciting and maintaining higher antibody levels to protect against poliovirus transmission and infection at the final stage of polio eradication in the global world. This study’s clinical trial registry number is NCT04224519. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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16 pages, 3424 KiB  

Open AccessArticle

Enhanced Downstream Processing for a Cell-Based Avian Influenza (H5N1) Vaccine

by Fang Li, Bo Liu, Yu Xiong, Zhegang Zhang, Qingmei Zhang, Ran Qiu, Feixia Peng, Xuanxuan Nian, Dongping Wu, Xuedan Li, Jing Liu, Ze Li, Hao Tu, Wenyi Wu, Yu Wang, Jiayou Zhang and Xiaoming Yang

Vaccines 2024, 12(2), 138; https://doi.org/10.3390/vaccines12020138 - 29 Jan 2024

Cited by 3 | Viewed by 2569

Abstract

H5N1 highly pathogenic avian influenza virus (HPAIV) infections pose a significant threat to human health, with a mortality rate of around 50%. Limited global approval of H5N1 HPAIV vaccines, excluding China, prompted the need to address safety concerns related to MDCK cell tumorigenicity. [...] Read more.

H5N1 highly pathogenic avian influenza virus (HPAIV) infections pose a significant threat to human health, with a mortality rate of around 50%. Limited global approval of H5N1 HPAIV vaccines, excluding China, prompted the need to address safety concerns related to MDCK cell tumorigenicity. Our objective was to improve vaccine safety by minimizing residual DNA and host cell protein (HCP). We developed a downstream processing method for the cell-based H5N1 HPAIV vaccine, employing Capto^TM Core 700, a multimodal resin, for polishing. Hydrophobic-interaction chromatography (HIC) with polypropylene glycol as a functional group facilitated the reversible binding of virus particles for capture. Following the two-step chromatographic process, virus recovery reached 68.16%. Additionally, HCP and DNA levels were reduced to 2112.60 ng/mL and 6.4 ng/mL, respectively. Western blot, high–performance liquid chromatography (HPLC), and transmission electron microscopy (TEM) confirmed the presence of the required antigen with a spherical shape and appropriate particle size. Overall, our presented two-step downstream process demonstrates potential as an efficient and cost-effective platform technology for cell-based influenza (H5N1 HPAIV) vaccines. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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15 pages, 4231 KiB  

Open AccessArticle

Protective MVA-ST Vaccination Robustly Activates T Cells and Antibodies in an Aged-Hamster Model for COVID-19

by Sabrina Clever, Lisa-Marie Schünemann, Federico Armando, Christian Meyer zu Natrup, Tamara Tuchel, Alina Tscherne, Malgorzata Ciurkiewicz, Wolfgang Baumgärtner, Gerd Sutter and Asisa Volz

Vaccines 2024, 12(1), 52; https://doi.org/10.3390/vaccines12010052 - 3 Jan 2024

Cited by 3 | Viewed by 2492

Abstract

Aging is associated with a decline in immune system functionality. So-called immunosenescence may impair the successful vaccination of elderly people. Thus, improved vaccination strategies also suitable for an aged immune system are required. Modified Vaccinia virus Ankara (MVA) is a highly attenuated and [...] Read more.

Aging is associated with a decline in immune system functionality. So-called immunosenescence may impair the successful vaccination of elderly people. Thus, improved vaccination strategies also suitable for an aged immune system are required. Modified Vaccinia virus Ankara (MVA) is a highly attenuated and replication-deficient vaccinia virus that has been established as a multipurpose viral vector for vaccine development against various infections. We characterized a recombinant MVA expressing a prefusion-stabilized version of SARS-CoV-2 S protein (MVA-ST) in an aged-hamster model for COVID-19. Intramuscular MVA-ST immunization resulted in protection from disease and severe lung pathology. Importantly, this protection was correlated with a potent activation of SARS-CoV-2 specific T-cells and neutralizing antibodies. Our results suggest that MVA vector vaccines merit further evaluation in preclinical models to contribute to future clinical development as candidate vaccines in elderly people to overcome the limitations of age-dependent immunosenescence. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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23 pages, 4711 KiB  

Open AccessReview

Amebicides against Acanthamoeba castellanii: The Impact of Organism Models Used in Amebicide Assays

by Leonardo Fernandes Geres, Elena Sartori, João Marcos dos Santos Neves, Danilo Ciccone Miguel and Selma Giorgio

Parasitologia 2024, 4(1), 15-37; https://doi.org/10.3390/parasitologia4010002 - 1 Jan 2024

Cited by 2 | Viewed by 3039

Abstract

Acanthamoeba castellanii is a free-living amoeba capable of causing keratitis in humans, with most cases related to contact lens wearers and surgical procedures. In addition, A. castellanii may cause pneumonia, granulomatous encephalitis, and skin lesions in immunocompromised individuals. Considering the lack of adequate treatment [...] Read more.

Acanthamoeba castellanii is a free-living amoeba capable of causing keratitis in humans, with most cases related to contact lens wearers and surgical procedures. In addition, A. castellanii may cause pneumonia, granulomatous encephalitis, and skin lesions in immunocompromised individuals. Considering the lack of adequate treatment for acanthamoebiasis, the aim of this review is to assess relevant original articles that covered the current arsenal of drugs and models of organisms used in the field of experimental A. castellanii infection that have been published within the last 5 years (2018–2023) in journals indexed by the following databases: Electronic Library Online (SciELO), PubMed, Medical Literature Analysis and Retrieval System Online (Medline), Latin American and Caribbean Literature in Health Sciences (Lilacs), Google Academic, and Capes Periodical Portal. Thirty articles were selected, and the main findings showed that the available therapeutics for acanthamoebiasis are still limited and nonspecific, and no innovations have occurred in the last few years. In terms of novel chemotherapeutic advances, the last findings have focused on the activity of natural products (plant-based extracts), nanoemulsions, coated particles, and photodynamic association against A. castellanii, without advancing from the bench to bedside perspective. The choice of a non-representative model system for acanthamoebiasis, as well as the limitations of studies in vivo, impairs the advancement of toxicity analyses. Efforts should be made to expand the model systems used, standardize tests for evaluating anti-A. castellanii drug candidates, and increase and support research groups focusing on the biology of A. castellanii and the pharmacology of acanthamoebiasis. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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13 pages, 2765 KiB  

Open AccessArticle

Anti-Hcp1 Monoclonal Antibody Is Protective against Burkholderia pseudomallei Infection via Recognizing Amino Acids at Asp95-Leu114

by Pan Wu, Chenglong Rao, Wenzheng Liu, Ziyuan Zhang, Dongqi Nan, Jiangao Chen, Minyang Wang, Yuan Wen, Jingmin Yan, Juanjuan Yue, Xuhu Mao and Qian Li

Pathogens 2024, 13(1), 43; https://doi.org/10.3390/pathogens13010043 - 31 Dec 2023

Cited by 1 | Viewed by 2282

Abstract

Melioidosis, a severe tropical illness caused by Burkholderia pseudomallei, poses significant treatment challenges due to limited therapeutic options and the absence of effective vaccines. The pathogen’s intrinsic resistance to numerous antibiotics and propensity to induce sepsis during acute infections further complicate management [...] Read more.

Melioidosis, a severe tropical illness caused by Burkholderia pseudomallei, poses significant treatment challenges due to limited therapeutic options and the absence of effective vaccines. The pathogen’s intrinsic resistance to numerous antibiotics and propensity to induce sepsis during acute infections further complicate management strategies. Thus, exploring alternative methods for prevention and treatment is crucial. Monoclonal antibodies (mAbs) have emerged as a promising strategy for the prevention and treatment of infectious diseases. This study focused on generating three mAbs (13F1, 14G11, and 15D9) targeting hemolysin-coregulated protein 1 (Hcp1), a protein involved in the type VI secretion system cluster 1 (T6SS1) of B. pseudomallei. Notably, pretreatment with 13F1 mAb significantly reduced the intracellular survival of B. pseudomallei and inhibited the formation of macrophage-derived multinucleated giant cells (MNGCs). This protective effect was also observed in vivo. We identified a sequence of amino acids (Asp95-Leu114) within Hcp1 as the likely binding site for 13F1 mAb. In summary, our findings reveal that 13F1 mAb counteracts infection by targeting Hcp1, offering potential new targets and insights for melioidosis prevention. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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4 pages, 652 KiB  

Open AccessEditorial

Successful Allergen-Specific Immunotherapy: Induction of Unresponsiveness by ‘Vaccination’

by Martin F. Bachmann, Monique Vogel and Daniel E. Speiser

Vaccines 2023, 11(12), 1852; https://doi.org/10.3390/vaccines11121852 - 14 Dec 2023

Cited by 1 | Viewed by 1729

Abstract

The mechanisms of action of allergen-specific immunotherapy (AIT) are often referred to as the induction of ‘tolerance’. However, immunological ‘tolerance’ is defined as an alteration in the function or composition of immune cells. For AIT, this is not always the case, because it [...] Read more.

The mechanisms of action of allergen-specific immunotherapy (AIT) are often referred to as the induction of ‘tolerance’. However, immunological ‘tolerance’ is defined as an alteration in the function or composition of immune cells. For AIT, this is not always the case, because it can also induce allergen-specific IgG antibodies that block allergic responses. To include all possible mechanisms that may mediate successful AIT, it is advantageous to use the scientific term ‘unresponsiveness’ instead of ‘tolerance’. In praxis, the term ‘vaccination’ is also appropriate, as AIT medications are specialized vaccines. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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13 pages, 570 KiB  

Open AccessArticle

Pathotypes and Phenotypic Resistance to Antimicrobials of Escherichia coli Isolates from One-Day-Old Chickens

by Katerina Nedbalcova, Jaroslav Bzdil, Aneta Papouskova, Monika Zouharova, Katarina Matiaskova, Kamil Stastny, Vladimir Sladecek, David Senk, Matej Petr and Petr Stolar

Pathogens 2023, 12(11), 1330; https://doi.org/10.3390/pathogens12111330 - 8 Nov 2023

Cited by 2 | Viewed by 1635

Abstract

The aim of this work was to describe the pathotypes of Escherichia coli strains isolated from one-day-old chickens, as well as the occurrence of resistance and multidrug resistance (MDR) in these strains. A total of 429 mixed swabs from 4290 one-day-old chicks were [...] Read more.

The aim of this work was to describe the pathotypes of Escherichia coli strains isolated from one-day-old chickens, as well as the occurrence of resistance and multidrug resistance (MDR) in these strains. A total of 429 mixed swabs from 4290 one-day-old chicks were examined between August 2021 and July 2023 (24 months) during routine point-of-destination inspections at 12 poultry farms in the Czech Republic. All samples were processed via cultivation methods using meat-peptone blood agar and Mc Conkey agar under aerobic conditions at 37 ± 1 °C for 18–24 h. The identification of the strains was performed using MALDI-TOF mass spectrometry. All confirmed strains of E. coli were screened via single or multiplex PCRs for the presence of genes encoding the virulence-associated factors iroN, cvaC, iss, felA, iutA, frz and tsh. Antimicrobial susceptibility tests were performed using the minimal inhibitory concentration (MIC) method, focusing on ampicillin, cefotaxime, tetracycline, doxycycline, enrofloxacin, florfenicol, amoxicillin with clavulanic acid and trimethoprim with sulfamethoxazole. A total of 321 E. coli strains (prevalence of 74.8%) were isolated, and 300 isolates were defined as avian pathogenic strains of E. coli (APEC) via multiplex PCR. Based on the defined virulence genes, the isolates were classified into 31 pathotypes. A total of 15.9% of the tested isolates were susceptible to all the tested antimicrobials. On the other hand, 20.5% of the isolates were identified as multidrug-resistant (8.7% of isolates were resistant to three antimicrobials, 7.3% to four antimicrobials, 3.6% to five antimicrobials and 0.9% to six antimicrobials). Monitoring pathogenic strains of E. coli in different animals and in the environment makes it possible to understand their spread in animal and human populations and, at the same time, reveal the sources of virulence and resistance genes. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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14 pages, 262 KiB  

Open AccessArticle

Development of a Novel Canine Parvovirus Vaccine Capable of Stimulating Protective Immunity in Four-Week-Old Puppies in the Face of High Levels of Maternal Antibodies

by Jacqueline Pearce, Norman Spibey, David Sutton and Ian Tarpey

Vaccines 2023, 11(9), 1499; https://doi.org/10.3390/vaccines11091499 - 18 Sep 2023

Cited by 7 | Viewed by 6931

Abstract

Many highly effective vaccines have been developed to protect dogs against disease caused by canine parvovirus, but despite this vaccine interference by maternally derived antibodies continues to cause immunisation failure. To help overcome this limitation we have developed a novel, recombinant canine parvovirus [...] Read more.

Many highly effective vaccines have been developed to protect dogs against disease caused by canine parvovirus, but despite this vaccine interference by maternally derived antibodies continues to cause immunisation failure. To help overcome this limitation we have developed a novel, recombinant canine parvovirus type 2c vaccine strain, based on the structural and non-structural elements of an established type 2 vaccine. This novel CPV-2c vaccine strain has unique efficacy in the field, it is able to induce sterilising immunity in naïve animals 3 days after vaccination and is able to overcome very high levels of maternally derived antibodies from 4 weeks of age—thus closing the immunity gap to canine parvovirus infection in young puppies. The vaccine strain, named 630a, has been combined with an established canine distemper virus Onderstepoort vaccine strain to produce a new bivalent vaccine (Nobivac DP PLUS), intended to immunise very young puppies in the face of high levels of maternally derived antibody. Here, we describe the onset of immunity and maternal antibody interference studies that support the unique efficacy of the strain, and present overdose studies in both dogs and cats that demonstrate the vaccine to be safe. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy)

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