Advances in Vaccines and Antimicrobial Therapy—2nd Edition

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Dear Colleagues,

This topic is a second edition of “Advances in Vaccines and Antimicrobial Therapy”. Our first edition has published 20 papers with a total of 37474 views. You can read the latest papers at: https://www.mdpi.com/topics/X66IH7XM49. Now we have set up a second edition and look forward to receiving more submissions.

The fields of prevention and treatment of infectious diseases have been gaining momentum after the outbreak 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 meta-analyses, 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. Raffaele D’Amelio
Dr. Roberto Paganelli
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biologics biologics	-	7.2	2021	31.4 Days	CHF 1200	Submit
Biomedicines biomedicines	3.9	6.8	2013	21 Days	CHF 2600	Submit
Biomolecules biomolecules	4.8	9.2	2011	17.9 Days	CHF 2700	Submit
Cells cells	5.2	10.5	2012	15.5 Days	CHF 2700	Submit
International Journal of Molecular Sciences ijms	4.9	9.0	2000	17.8 Days	CHF 2900	Submit
Microorganisms microorganisms	4.2	7.7	2013	20 Days	CHF 2700	Submit
Pathogens pathogens	3.3	6.8	2012	14.1 Days	CHF 2200	Submit
Vaccines vaccines	3.4	9.9	2013	18.1 Days	CHF 2700	Submit

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Published Papers (8 papers)

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All Biomolecules Cells IJMS Pathogens Vaccines Biologics Microorganisms Biomedicines

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22 pages, 4783 KB  

Open AccessArticle

Engineering a Modular PapMV Nanoparticle Vaccine: Comparative Efficacy of a Covalent and a Non-Covalent N-Antigen Vaccine Against Emerging SARS-CoV-2 Variants

by Léa-J. Blanchette, Marilène Bolduc, Tekeleselassie Woldemariam, Mitra Yousefi, Henintsoa Rabezanahary, Santa-M. Olivera-Ugarte, Caroline Garneau, Myriam Angers, Rong Shi, Louis Flamand, Mariana Baz, Silvia Vidal, Darryl Falzarano, Jean-François Lemay and Denis Leclerc

Vaccines 2026, 14(4), 349; https://doi.org/10.3390/vaccines14040349 - 15 Apr 2026

Viewed by 451

Abstract

Background: Despite the effectiveness of current SARS-CoV-2 vaccines, the genetic variability of the viral target has led to the emergence of variants capable of evading vaccine-induced protection. To ensure broader and more durable protection, we investigated the efficacy of a novel vaccine [...] Read more.

Background: Despite the effectiveness of current SARS-CoV-2 vaccines, the genetic variability of the viral target has led to the emergence of variants capable of evading vaccine-induced protection. To ensure broader and more durable protection, we investigated the efficacy of a novel vaccine strategy. Methods: This vaccine utilizes the highly conserved nucleocapsid (N) protein as its primary antigen, rather than the spike (S) protein. It incorporates the Papaya Mosaic Virus (PapMV) nanoparticle, a Toll-like receptor (TLR) 7/8 agonist with intrinsic adjuvant properties, as a vaccine platform. Results: The vaccine formulations, comprising PapMV nanoparticles and the N antigen covalently or non-covalently attached to the PpaMV nano, generated robust humoral (antibody) and cellular (T-cell) immune responses. Protective efficacy was evaluated in K18-hACE2 transgenic mice challenged with either the ancestral SARS-CoV-2 strain or the Omicron XBB.1.5 variant. In both cases, the vaccine significantly reduced inflammation and viral titers in the lungs of vaccinated animals. Conclusions: These results highlight the potential of this PapMV-N vaccine to induce broad protection against diverse SARS-CoV-2 variants. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy—2nd Edition)

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18 pages, 2962 KB  

Open AccessArticle

Fine-Mapping and Protective Analysis of Immunodominant Linear B-Cell Epitopes of FimA Antigen of Klebsiella Pneumoniae

by Pengju Yan, Longlong Chen, Guangyang Ming, Zhifu Chen, Qiang Gou, Yue Yuan, Haiming Jing, Ping Luo, Jinyong Zhang and Zhuo Zhao

Vaccines 2026, 14(4), 347; https://doi.org/10.3390/vaccines14040347 - 15 Apr 2026

Viewed by 395

Abstract

Background/Objectives: Klebsiella pneumoniae (K. pneumoniae) is a leading cause of serious hospital-acquired and community-acquired infections, with limited treatment options, especially for immunocompromised and critically ill patients. No licensed vaccine is currently available. The FimA antigen, a key fimbrial subunit essential [...] Read more.

Background/Objectives: Klebsiella pneumoniae (K. pneumoniae) is a leading cause of serious hospital-acquired and community-acquired infections, with limited treatment options, especially for immunocompromised and critically ill patients. No licensed vaccine is currently available. The FimA antigen, a key fimbrial subunit essential for bacterial adhesion and invasion, represents a promising vaccine target. However, little is known about the immunodominant antibody responses against invasive K. pneumoniae. This study aimed to evaluate the immunogenicity and protective efficacy of recombinant FimA protein, to fine-map its immunodominant linear B-cell epitopes, and to assess the individual and combined protective capacity of these epitopes against both standard and clinically isolated K. pneumoniae strains. Methods: A murine model of lethal K. pneumoniae challenge was used. Recombinant FimA protein was administered to evaluate immunogenicity and protective efficacy. Immunodominant linear B-cell epitopes were identified by overlapping peptide ELISA using immune antisera. The identified epitopes were synthesized and conjugated to keyhole limpet hemocyanin (KLH). Mice were immunized with individual epitope-KLH conjugates or a mixture of all four, then challenged with the standard strain ATCC700721 or with multiple clinical isolates of distinct multilocus sequence types (MLST). Epitope-specific antibody responses (total IgG and IgG subclasses) and survival rates were measured. Results: Immunization with full-length recombinant FimA conferred 90% protection against lethal challenge with the standard strain ATCC700721 and induced robust IgG1-dominant antibody responses. Four novel immunodominant linear B-cell epitopes were identified: FimA_97–114, FimA_103–120, FimA_109–126, and FimA_145–160. Structural mapping revealed that the first three epitopes reside within the α-helical region, while FimA_145–160 is located in the β-sheet domain. These epitopes are highly conserved, exhibiting 100% sequence identity across 36 diverse K. pneumoniae strains. Among individual epitope-KLH conjugates, FimA_109–126-KLH induced the highest epitope-specific antibody titers, followed by FimA_103–120-KLH. Immunization with a mixture of all four epitope-KLH conjugates elicited significant cross-protection against multiple clinical isolates, achieving survival rates of 60%, 50%, 50%, and 40% against strains 10CYZ, 13LGY, 19ZXQ, and 22CZY, respectively. Protective immunity was primarily associated with IgG1 subtype responses. Conclusions: This study provides the first fine-mapping and protective evaluation of immunodominant linear B-cell epitopes within K. pneumoniae FimA. The identification of highly conserved, functionally relevant B-cell epitopes and the demonstration of cross-protection conferred by a multi-epitope formulation underscore the potential of FimA-based epitope-driven vaccines. These findings offer a promising strategy for the development of broadly protective vaccines against K. pneumoniae infections. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy—2nd Edition)

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19 pages, 15696 KB  

Open AccessArticle

From Phage Display to Yeast Secretion: Developing Fc-Fused Nanobodies Against Influenza Virus

by Mei Wang, Shujun Li, Yong Li, Xiaomei Xia, Yan Zhang, Ning Cao, Yuanfang Li, Yijia Liu, Sheng Zhang, Lilin Zhang and Jinhai Huang

Cells 2026, 15(8), 655; https://doi.org/10.3390/cells15080655 - 8 Apr 2026

Viewed by 657

Abstract

Avian influenza infections cause substantial economic losses in the poultry industry and raise public health concerns due to viral adaptation and cross-species transmission. The frequent antigenic drift of influenza viruses further complicates the prevention and treatment of avian respiratory infections. In this study, [...] Read more.

Avian influenza infections cause substantial economic losses in the poultry industry and raise public health concerns due to viral adaptation and cross-species transmission. The frequent antigenic drift of influenza viruses further complicates the prevention and treatment of avian respiratory infections. In this study, we generated high-affinity heavy-chain variable domain (VHH) nanobodies from naïve alpaca/camelid VHH libraries using phage display combined with H9N2 influenza A virus (IAV)-infected Madin-Darby Canine Kidney (MDCK) cells. Based on binding affinity and neutralization potential, we identified seven hemagglutinin (HA)-specific and two neuraminidase (NA)-specific VHHs. Molecular docking predicted the interaction sites of HA-specific VHHs (L1-2, L1-4, A5) and NA-specific VHHs (L1-3, L2-2), providing mechanistic insights. Notably, the three HA-specific VHHs (L1-2, L1-4, A5) showed cross-reactivity to representative HA subtypes (H1, H3, and influenza B), indicating recognition of conserved epitopes across divergent influenza strains. For the first time, these camelid nanobodies were fused to the chicken IgY Fc domain, and the expression cassette was integrated into the Saccharomyces cerevisiae genome, achieving a secretion yield of 15–20 mg/L of VHH-Fc antibodies. Experimental validation confirmed that the three HA-specific VHHs-Fc constructs effectively blocked viral infection, while the two NA-specific VHH-Fc constructs (L1-3, L2-2) inhibited NA activity, demonstrating the functional efficacy of the yeast-secreted VHH–IgY Fc platform. This novel IgY Fc fusion approach offers a scalable platform with enhanced stability, extended circulation potential, and applicability in poultry. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy—2nd Edition)

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36 pages, 1452 KB  

Open AccessReview

Tularemia: Historical Perspectives and Current Challenges of a Re-Emerging Zoonosis

by Maria Di Spirito, Chiara Pascolini, Simonetta Salemi, Ferdinando Spagnolo, Vincenzo Luca, Filippo Molinari, Orr Rozov, Florigio Lista, Raffaele D’Amelio and Silvia Fillo

Biomedicines 2026, 14(3), 695; https://doi.org/10.3390/biomedicines14030695 - 17 Mar 2026

Viewed by 675

Abstract

Tularemia is a plague-like, potentially fatal zoonosis caused by the coccobacillus Francisella tularensis. It was discovered at the beginning of the last century in the United States and was soon recognized in Japan and in the former Soviet Union as the cause [...] Read more.

Tularemia is a plague-like, potentially fatal zoonosis caused by the coccobacillus Francisella tularensis. It was discovered at the beginning of the last century in the United States and was soon recognized in Japan and in the former Soviet Union as the cause of clinical conditions that had been known for one and two centuries, respectively. More than 250 animal species are susceptible to infection, with rodents and lagomorphs serving as key reservoirs, and several vectors may transmit the disease, mainly ticks and mosquitoes. Humans are incidental hosts and are infected primarily by two F. tularensis subspecies, tularensis and holarctica: the former is more severe and is found almost exclusively in North America, whereas the latter is distributed throughout the Northern Hemisphere, mainly in Europe and Asia. Tularemia is highly infectious; therefore, diagnostic cultures should be handled in biosafety level 3 laboratories. Nevertheless, interhuman transmission is exceedingly rare. Although tularemia is relatively uncommon, it shows a re-emerging pattern at the global level, particularly in Europe. As with plague, mitigation may be more effectively achieved through a One Health approach. Neither approved vaccines nor therapeutic antibodies are currently available, whereas aminoglycoside, tetracycline, and quinolone antibiotics are effective. Owing to its high infectivity, its ease of transmission by inhalation, its clinical severity, with a prolonged and debilitating course, and its potential lethality, F. tularensis has long been considered a potential biological weapon, particularly if antibiotic-resistant strains were used. Although natural antibiotic resistance has not been described to date, research programs aimed at obtaining resistant strains have been conducted. It has been suggested that the disease was already present in the Middle East during the second millennium BC; should this hypothesis be confirmed by paleogenomic studies, plague and tularemia would have coexisted for more than three millennia, with plague masking the less severe tularemia. Many challenges related to tularemia are still unresolved. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy—2nd Edition)

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21 pages, 5951 KB  

Open AccessArticle

Design of a Multi-Epitope Vaccine Against Ovine Pasteurella multocida Using Immunoinformatics Strategies

by Yanjie Qiao, Aodi Wu, Honghuan Li, Youquan Zhuang, Qiang Fu, Li Yang and Huijun Shi

Microorganisms 2026, 14(3), 656; https://doi.org/10.3390/microorganisms14030656 - 13 Mar 2026

Viewed by 2214

Abstract

This study aimed to design a multi-epitope vaccine (MEV) against Pasteurella multocida (Pm) using immunoinformatics approaches. Based on four conserved outer membrane proteins (OmpA; OmpH; PlpEand LolA), 15 immunodominant epitopes were identified, including 8 CTL epitopes, 3 HTL epitopes, and 4 B-cell epitopes. [...] Read more.

This study aimed to design a multi-epitope vaccine (MEV) against Pasteurella multocida (Pm) using immunoinformatics approaches. Based on four conserved outer membrane proteins (OmpA; OmpH; PlpEand LolA), 15 immunodominant epitopes were identified, including 8 CTL epitopes, 3 HTL epitopes, and 4 B-cell epitopes. A vaccine construct was developed by incorporating RGD and PADRE adjuvant sequences. Computational analyses indicated that the vaccine possesses favorable physicochemical properties and structural stability. The molecular docking and normal mode analyses reveal a potential binding interface between the basis and TLR2/TLR4, with a computed binding energy of −10.1 kcal/mol for TLR4, suggesting a possible preferential interaction. Immune simulation predicted the vaccine could effectively elicit responses from B cells, T cells, and key cytokines such as IFN-γ. Additionally, the vaccine sequence was successfully cloned into the pET-28a (+) expression vector, facilitating future recombinant expression. This study provides a theoretical foundation for developing a safe and effective subunit vaccine against Pm. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy—2nd Edition)

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20 pages, 4305 KB  

Open AccessArticle

Novel Enzymes for Biologics with Hydrolytic Activity Against Thiolactones: Computational, Catalytic and Antimicrobial Study

by Maksim Domnin, Anastasia Sarapina, Aysel Aslanli, Olga Senko and Elena Efremenko

Biologics 2025, 5(4), 34; https://doi.org/10.3390/biologics5040034 - 3 Nov 2025

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Abstract

Background: Various thiolactones are known as biologically active compounds, capable of stimulating the development of several human diseases and quorum sensing of Gram–positive bacteria. The enzymatic hydrolysis of thiolactones represents a promising approach to preventing their action. Methods: Thirteen enzymes, including various lactonases [...] Read more.

Background: Various thiolactones are known as biologically active compounds, capable of stimulating the development of several human diseases and quorum sensing of Gram–positive bacteria. The enzymatic hydrolysis of thiolactones represents a promising approach to preventing their action. Methods: Thirteen enzymes, including various lactonases and serine hydrolases were studied in this work using several substrates including the homocysteine thiolactone (HTL), and its derivatives the N–acetylhomocysteine thiolactone (C₂–HTL) and the isobutyryl–homocystein thiolactone (i–but–HTL). The potential interactions of the ligands with the surface of enzymes molecules were predicted in silico using computational modeling and checked in wet experiments in vitro. Results: Based on the data obtained several enzymes were selected with localization of the thiolactones near their active sites, indicating the possibility of effective catalysis. The lactonase (AiiA), metallo-β-lactamase (NDM-1) and the organophosphate hydrolase with hexahistidine tag (His₆–OPH) were among them. Determination of catalytic characteristics of enzymes in the hydrolytic reactions with the HTL and the C₂–HTL revealed the maximal value of catalytic efficiency constant for the NDM-1 in the hydrolysis of the HTL (826 M⁻¹ s⁻¹). The maximal activity in the hydrolysis of C₂–HTL was established for AiiA (137 M⁻¹ s⁻¹). The polyaspartic (PLD₅₀) and the polyglutamic (PLE₅₀) acids were used to obtain polyelectrolyte complexes with enzymes. The further combination of these complexes with the clotrimazole and polymyxin B possessing antimicrobial properties resulted in notable improvement of their action in relation to Staphylococcus cells. Conclusions: It was revealed that the antimicrobial activity of the polymyxin B is enhanced by 9–10 times against bacteria and yeast when combined with the His₆–OPH polyelectrolyte complexes. The antimicrobial activity of clotrimazole was increased by ~7 times against Candida tropicalis cells in the case of the AiiA/PLE₅₀/Clotrimazole combination. These results make the obtained biology attractive and promising for their further advancement to practical application. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy—2nd Edition)

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18 pages, 1962 KB  

Open AccessArticle

Baculovirus-Displayed ASFV Epitope-Composite Protein Elicits Potent Immune Responses

by Wenkai Zhang, Xing Yang, Xingyu Chen, Jiaxin Jin, Yuanyuan Zhang, Lele Gong, Shuai Zhang, Xuyang Zhao, Yongkun Du, Yanan Wu, Aijun Sun and Guoqing Zhuang

Microorganisms 2025, 13(11), 2468; https://doi.org/10.3390/microorganisms13112468 - 29 Oct 2025

Viewed by 968

Abstract

African swine fever (ASF), caused by the African swine fever virus (ASFV), is an acute, febrile, highly contagious, and lethal disease that poses a severe threat to the global pig farming industry. Currently, no globally recognized, safe, and effective commercial ASF vaccine has [...] Read more.

African swine fever (ASF), caused by the African swine fever virus (ASFV), is an acute, febrile, highly contagious, and lethal disease that poses a severe threat to the global pig farming industry. Currently, no globally recognized, safe, and effective commercial ASF vaccine has been developed, making vaccination a crucial strategy for outbreak control. The ASFV structural proteins p72, p30, and p54 are key targets for vaccine development. In this study, we developed a novel baculovirus vector-based system for surface display of a recombinant protein comprising epitopes from p72, p30, and p54. Upon infection, the recombinant protein was expressed and anchored on the plasma membrane of Sf-9 cells. Purified virus analysis revealed that the Bac-recombinant protein enhanced gene delivery and transgene expression in mammalian cells compared to the Bac-Wild Type (Bac-WT). In a murine model, the Bac-recombinant protein induced significantly higher IFN-γ and IL-4 levels than Bac-p30 and the negative control. However, further evaluation in swine models is required to confirm its protective potential against ASFV. Furthermore, it also elicited a robust antibody response, generating high-titer Bac-recombinant protein-specific antibodies. Therefore, these findings suggest that the ASFV Bac-recombinant protein is a promising candidate for a vector-based vaccine. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy—2nd Edition)

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12 pages, 439 KB  

Open AccessArticle

A Single-Center Retrospective Study on Early Treatment for COVID-19 in Solid Organ Transplant Recipients During the Omicron Era: Outcomes and SARS-CoV-2 Viral Kinetics

by Eugenia Milozzi, Elisa Biliotti, Alessandro Caioli, Valentina Mazzotta, Laura Loiacono, Silvia Meschi, Alessia Rianda, Andrea Antinori, Fabrizio Maggi and Gianpiero D’Offizi

Microorganisms 2025, 13(8), 1872; https://doi.org/10.3390/microorganisms13081872 - 11 Aug 2025

Viewed by 854

Abstract

Solid organ transplant recipients (SOTRs) are at high risk of severe coronavirus disease 2019 (COVID-19), therefore early treatment of mild infections is crucial to prevent increased morbidity and mortality. The effectiveness of early treatment in SOTRs has yet to be fully characterized due [...] Read more.

Solid organ transplant recipients (SOTRs) are at high risk of severe coronavirus disease 2019 (COVID-19), therefore early treatment of mild infections is crucial to prevent increased morbidity and mortality. The effectiveness of early treatment in SOTRs has yet to be fully characterized due to the emergence of new SARS-CoV-2 variants and to COVID-19 vaccination implementation. The aim of this single-center retrospective study is to evaluate the outcomes, safety and impact on SARS-CoV-2 viral load kinetics of COVID-19 early treatment in SOTRs. The study includes 80 SOTRs with a laboratory-confirmed diagnosis of symptomatic SARS-CoV-2 infection enrolled between January and October 2022 and treated with either monoclonal antibodies or antivirals. All patients received COVID-19 vaccination and 68.8% of them showed detectable levels of anti-spike (S) antibodies. The occurrence of clinical events (hospitalization, intensive care unit admission, or death) was assessed within 30 days after treatment initiation. The quantification of SARS-CoV-2 viral load were performed at baseline and at day-7. The rate of hospitalization was 2.5% [0.3–9%] and no deaths occurred. All patients completed treatment with no serious adverse events. Median viral load decrease was 0.48 [0.26–0.69] log₂ cycle threshold (ct) values, with no significant differences between SOTRs treated with monoclonal antibodies and those treated with antivirals. Viral load decrease was significantly associated with positive anti-s serology at baseline ($\beta$ = 0.196, p = 0.01), number of days between symptom onset and treatment ($\beta$ = 0.05, p = 0.03) and the number of comorbidities ($\beta$ = −0.05, p = 0.03). We provide evidence of real-world effectiveness of early therapy in SOTRs infected with SARS-CoV-2 and demonstrate the relevant role of humoral response to vaccination in enhancing early viral load decay during treatment. Full article

(This article belongs to the Topic Advances in Vaccines and Antimicrobial Therapy—2nd Edition)

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