The power of microbial life for the transformation towards a sustainable planet: key messages from the 2024 IUMS Congress in Florence, the city of the Renaissance.

The 2024 International Union of Microbiological Societies Congress was held in Florence, the city of Renaissance. The theme was to increase the awareness of the power of microbial life, recognizing that it can lead the transformation towards a sustainable planet. The meeting gathered over 1400 experts from more than 90 countries and focused on the transformative potential of microbiology in addressing global challenges and aligning microbial science with the Sustainable Development Goals.

The Story behind the Science: The discovery of CagA, the first tumorigenic bacterial protein.

In this article, we reconstruct the history of the science that led to the discovery of CagA, the protein that causes gastric cancer, where teams in the United States and Italy made independent observations that ultimately merged. We also honor the memory of Antonello Covacci, who played an important role in this discovery and passed away prematurely in 2023.

Challenges and opportunities in mRNA vaccine development against bacteria.

The global surge in antimicrobial resistance presents a critical threat to public health, emphasizing the urgent need for the development of new and more effective bacterial vaccines. Since the success of mRNA vaccines during the COVID-19 pandemic, this vaccine strategy has rapidly advanced, with most efforts focused on cancer immunotherapy and targeting viral pathogens. Recently, mRNA vaccines have entered the early phases of clinical development for bacterial diseases.

A multifunctional anti-O-Antigen human monoclonal antibody protects against infection in vivo.

Shigellosis is a global public health challenge that mostly affects low- and middle-income countries and causes considerable morbidity and mortality among children under 5 y of age. Multi- and extensively drug-resistant strains associated with recent outbreaks in high-income countries exacerbate the problem and have prompted the World Health Organization to include spp. among the high-risk pathogens for which novel prophylactic and therapeutic tools are urgently needed.

Human monoclonal antibodies targeting subdominant meningococcal antigens confer cross-protection against gonococcus.

Gonococcus, a bacterium resistant to most antibiotics, causes more than 80 million cases of gonorrhea annually and is considered a high-priority pathogen by the World Health Organization. Recently, vaccine development prospects were boosted by reports that licensed meningococcus serogroup B (MenB) vaccines provided partial protection against gonococcal infection. To determine antigens responsible for cross-protection, memory B cells isolated from 4CMenB-vaccinated volunteers were single cell-sorted to identify antibodies that kill gonococcus in a bactericidal assay.

Vaccinology in the artificial intelligence era.

Artificial intelligence (AI) has already transformed vaccine antigen design and could transform the entire vaccinology pipeline, including immune responses and emerging infectious disease prediction, manufacturing and regulatory processes, clinical trial design and implementation, and vaccine access and equity. However, realizing the promise of AI for vaccinology requires more high-quality data.

State of the Art and Emerging Technologies in Vaccine Design for Respiratory Pathogens.

In this review, we present the efforts made so far in developing effective solutions to prevent infections caused by seven major respiratory pathogens: influenza virus, respiratory syncytial virus (RSV), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), , (), , and . Advancements driven by the recent coronavirus disease 2019 (COVID-19) crisis have largely focused on viruses, but effective prophylactic solutions for bacterial pathogens are also needed, especially in light of the antimicrobial resistance (AMR) phenomenon. Here, we discuss various innovative key technologies that can help address this critical need, such as (a) the development of Lung-on-Chip ex vivo models to gain a better understanding of the pathogenesis process and the host-microbe interactions; (b) a more thorough investigation of the mechanisms behind mucosal immunity as the first line of defense against pathogens; (c) the identification of correlates of protection (CoPs) which, in conjunction with the Reverse Vaccinology 2.

Scientists' call to action: Microbes, planetary health, and the Sustainable Development Goals.

Microorganisms, including bacteria, archaea, viruses, fungi, and protists, are essential to life on Earth and the functioning of the biosphere. Here, we discuss the key roles of microorganisms in achieving the United Nations Sustainable Development Goals (SDGs), highlighting recent and emerging advances in microbial research and technology that can facilitate our transition toward a sustainable future. Given the central role of microorganisms in the biochemical processing of elements, synthesizing new materials, supporting human health, and facilitating life in managed and natural landscapes, microbial research and technologies are directly or indirectly relevant for achieving each of the SDGs.

Transforming vaccinology.

The COVID-19 pandemic placed the field of vaccinology squarely at the center of global consciousness, emphasizing the vital role of vaccines as transformative public health tools. The impact of vaccines was recently acknowledged by the award of the 2023 Nobel Prize in Physiology or Medicine to Katalin Kariko and Drew Weissman for their seminal contributions to the development of mRNA vaccines. Here, we provide a historic perspective on the key innovations that led to the development of some 27 licensed vaccines over the past two centuries and recent advances that promise to transform vaccines in the future.

Next generation of "magic bullets", solutions from the microbial pangenome.

Identification of a toxic agent that—like a sniper—would be capable of targeting pathogenic bacteria and effectively discriminating between “good” and “evil” cells has long been the holy grail of drug discovery. The theory of magic bullet, first pioneered by Paul Ehrlich in the early 1900, has represented since then a “ in immunological research against infectious diseases. Salvarsan, the first arsenic-based drug against syphilis, was the first example showing that this concept was in fact a realistic goal.

Antigenic sin and multiple breakthrough infections drive converging evolution of COVID-19 neutralizing responses.

Understanding the evolution of the B cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is fundamental to design the next generation of vaccines and therapeutics. We longitudinally analyze at the single-cell level almost 900 neutralizing human monoclonal antibodies (nAbs) isolated from vaccinated people and from individuals with hybrid and super hybrid immunity (SH), developed after three mRNA vaccine doses and two breakthrough infections. The most potent neutralization and Fc functions against highly mutated variants belong to the SH cohort.

SARS-CoV-2 JN.1 variant evasion of IGHV3-53/3-66 B cell germlines.

The severe acute respiratory syndrome coronavirus 2 variant JN.1 recently emerged as the dominant variant despite having only one amino acid change on the spike (S) protein receptor binding domain (RBD) compared with the ancestral BA.2.

Neisserial adhesin A (NadA) binds human Siglec-5 and Siglec-14 with high affinity and promotes bacterial adhesion/invasion.

Neisserial adhesin A (NadA) is a meningococcal surface protein included as recombinant antigen in 4CMenB, a protein-based vaccine able to induce protective immune responses against serogroup B (MenB). Although NadA is involved in the adhesion/invasion of epithelial cells and human myeloid cells, its function in meningococcal physiology is still poorly understood. To clarify the role played by NadA in the host-pathogen interaction, we sought to identify its cellular receptors.

Licensed H5N1 vaccines generate cross-neutralizing antibodies against highly pathogenic H5N1 clade 2.3.4.4b influenza virus.

The emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.

4CMenB journey to the 10-year anniversary and beyond.

The 4-component meningococcal serogroup B (MenB) vaccine, 4CMenB, the first broadly protective, protein-based MenB vaccine to be licensed, is now registered in more than 50 countries worldwide. Real-world evidence (RWE) from the last decade confirms its effectiveness and impact, with infant immunization programs showing vaccine effectiveness of 71-95% against invasive MenB disease and cross-protection against non-B serogroups, including a 69% decrease in serogroup W cases in 4CMenB-eligible cohorts in England. RWE from different countries also demonstrates the potential for additional moderate protection against gonorrhea in adolescents.

The economic case for scaling up health research and development: Lessons from the COVID-19 pandemic.

In response to the COVID-19 pandemic, governments directly funded vaccine research and development (R&D), quickly leading to multiple effective vaccines and resulting in enormous health and economic benefits to society. We develop a simple economic model showing this feat could potentially be repeated for other health challenges. Based on inputs from the economic and medical literatures, the model yields estimates of optimal R&D spending on treatments and vaccines for known diseases.

Safety and Immunogenicity of a 4-Component Generalized Modules for Membrane Antigens Shigella Vaccine in Healthy European Adults: Randomized, Phase 1/2 Study.

Background: We report data from stage 1 of an ongoing 2-staged, phase 1/2 randomized clinical trial with a 4-component generalized modules for membrane antigens-based vaccine against Shigella sonnei and Shigella flexneri 1b, 2a, and 3a (altSonflex1-2-3; GSK).

Methods: Europeans aged 18-50 years (N = 102) were randomized (2:1) to receive 2 injections of altSonflex1-2-3 or placebo at 3- or 6-month interval. Safety and immunogenicity were assessed at prespecified time points.

Functional diversification of innate and inflammatory immune responses mediated by antibody fragment crystallizable activities against SARS-CoV-2.

Monoclonal antibodies (mAb) targeting the SARS-CoV-2 Spike (S) glycoprotein have been exploited for the treatment of severe COVID-19. In this study, we evaluated the immune-regulatory features of two neutralizing anti-S mAbs (nAbs), named J08 and F05, with wild-type (WT) conformation or silenced Fc functions. In the presence of D614G SARS-CoV-2, WT nAbs enhance intracellular viral uptake in immune cells and amplify antiviral type I Interferon and inflammatory cytokine and chemokine production without viral replication, promoting the differentiation of CD16 inflammatory monocytes and innate/adaptive PD-L1 and PD-L1CD80 plasmacytoid Dendritic Cells.