Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection - Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug Resistance.

In April 1984, 40 years ago, the Secretary of the US Department of Health and Human Services announced that Dr. Robert Gallo and his colleagues at the National Cancer Institute (NCI) had confirmed the cause of acquired immunodeficiency syndrome (AIDS) as a retrovirus, which became known as human immunodeficiency virus (HIV) in 1986. For the past 40 years, prevention and cure of HIV infection have been the dual 'holy grail' sought but still not achieved. By the beginning of 2024, the World Health Organization (WHO) estimated that in the past 40 years, between 65.0 million and 113.0 million people have been infected with HIV, and between 32.9 million and 51.3 million people have died from HIV infection. On 29 February 2024, the WHO published an updated report in response to increasing reports of HIV drug resistance (HIVDR). Currently, HIV vaccines in development are in early-stage clinical trials. People with HIV are more likely to develop tuberculosis, with increasing rates of antimicrobial resistance. MTBVAC is the first live attenuated vaccine to prevent Mycobacterium tuberculosis infection, with phase 2a safety and efficacy clinical trial data expected at the end of 2024. This editorial aims to summarize the current challenges and hopes for developing vaccines to prevent HIV infection and approaches to overcome antiretroviral drug resistance as a cure for HIV/AIDS.

Epidemiology, pathogenesis, immune evasion mechanism and vaccine development of porcine Deltacoronavirus.

Coronaviruses have been identified as pathogens of gastrointestinal and respiratory diseases in humans and various animal species. In recent years, the global spread of new coronaviruses has had profound influences for global public health and economies worldwide. As highly pathogenic zoonotic viruses, coronaviruses have become the focus of current research. Porcine Deltacoronavirus (PDCoV), an enterovirus belonging to the family of coronaviruses, has emerged on a global scale in the past decade and significantly influenced the swine industry. Moreover, PDCoV infects not only pigs but also other species, including humans, chickens and cattles, exhibiting a broad host tropism. This emphasizes the need for in-depth studies on coronaviruses to mitigate their potential threats. In this review, we provided a comprehensive summary of the current studies on PDCoV. We first reviewed the epidemiological investigations on the global prevalence and distribution of PDCoV. Then, we delved into the studies on the pathogenesis of PDCoV to understand the mechanisms how the virus impacts its hosts. Furthermore, we also presented some exploration studies on the immune evasion mechanisms of the virus to enhance the understanding of host-virus interactions. Despite current limitations in vaccine development for PDCoV, we highlighted the inhibitory effects observed with certain substances, which offers a potential direction for future research endeavors. In conclusion, this review summarized the scientific findings in epidemiology, pathogenesis, immune evasion mechanisms and vaccine development of PDCoV. The ongoing exploration of potential vaccine candidates and the insights gained from inhibitory substances have provided a solid foundation for future vaccine development to prevent and control diseases associated with PDCoV.

Anti-neuraminidase immunity in the combat against influenza.

INTRODUCTION: Anti-neuraminidase (NA) immunity correlates with the protection against influenza virus infection in both human and animal models. The aim of this review is to better understand the mechanism of anti-NA immunity, and also to evaluate the approaches on developing NA-based influenza vaccines or enhancing immune responses against NA for current influenza vaccines. AREAS COVERED: In this review, the structure of influenza neuraminidase, the contribution of anti-NA immunity to protection, as well as the efforts and challenges of targeting the immune responses to NA were discussed. We also listed some of the newly discovered anti-NA monoclonal antibodies and discussed their contribution in therapeutic as well as the antigen design of a broadly protective NA vaccine. EXPERT OPINION: Targeting the immune response to both HA and NA may be critical for achieving the optimal protection since there are different mechanisms of HA and NA elicited protective immunity. Monoclonal antibodies (mAbs) that target the conserved protective lateral face or catalytic sites are effective therapeutics. The epitope discovery using monoclonal antibodies may benefit NA-based vaccine elicited broadly reactive antibody responses. Therefore, the potential for a vaccine that elicits cross-reactive antibodies against neuraminidase is a high priority for next-generation influenza vaccines.

Exploring HIV Vaccine Progress in the Pre-Clinical and Clinical Setting: From History to Future Prospects.

The human immunodeficiency virus (HIV) continues to pose a significant global health challenge, with millions of people affected and new cases emerging each year. While various treatment and prevention methods exist, including antiretroviral therapy and non-vaccine approaches, developing an effective vaccine remains the most crucial and cost-effective solution to combating the HIV epidemic. Despite significant advancements in HIV research, the HIV vaccine field has faced numerous challenges, and only one clinical trial has demonstrated a modest level of efficacy. This review delves into the history of HIV vaccines and the current efforts in HIV prevention, emphasizing pre-clinical vaccine development using the non-human primate model (NHP) of HIV infection. NHP models offer valuable insights into potential preventive strategies for combating HIV, and they play a vital role in informing and guiding the development of novel vaccine candidates before they can proceed to human clinical trials.

Application of CRISPR-cas-based technology for the identification of tuberculosis, drug discovery and vaccine development.

Tuberculosis (TB), which caused by Mycobacterium tuberculosis, is the leading cause of death from a single infectious agent and continues to be a major public health burden for the global community. Despite being the only globally licenced prophylactic vaccine, Bacillus Calmette-Guérin (BCG) has multiple deficiencies, and effective diagnostic and therapeutic options are limited. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) is an adaptive immune system that is found in bacteria and has great potential for the development of novel antituberculosis drugs and vaccines. In addition, CRISPR-Cas is currently recognized as a prospective tool for the development of therapies for TB infection with potential diagnostic and therapeutic value, and CRISPR-Cas may become a viable tool for eliminating TB in the future. Herein, we systematically summarize the current applications of CRISPR-Cas-based technology for TB detection and its potential roles in drug discovery and vaccine development.

Lymphatic distribution considerations for subunit vaccine design and development.

Subunit vaccines are an important platform for controlling current and emerging infectious diseases. The lymph nodes are the primary site generating the humoral response and delivery of antigens to these sites is critical to effective immunization. Indeed, the duration of antigen exposure within the lymph node is correlated with the antibody response. While current licensed vaccines are typically given through the intramuscular route, injecting vaccines subcutaneously allows for direct access to lymphatic vessels and therefore can enhance the transfer of antigen to the lymph nodes. However, protein subunit antigen uptake into the lymph nodes is inefficient, and subunit vaccines require adjuvants to stimulate the initial immune response. Therefore, formulation strategies have been developed to enhance the exposure of subunit proteins and adjuvants to the lymph nodes by increasing lymphatic uptake or prolonging the retention at the injection site. Given that lymph node exposure is a crucial consideration in vaccine design, in depth analyses of the pharmacokinetics of antigens and adjuvants should be the focus of future preclinical and clinical studies. This review will provide an overview of formulation strategies for targeting the lymphatics and prolonging antigen exposure and will discuss pharmacokinetic evaluations which can be applied toward vaccine development.

Immune Epitopes of SARS-CoV-2 Spike Protein and Considerations for Universal Vaccine Development.

Despite the success of global vaccination programs in slowing the spread of COVID-19, these efforts have been hindered by the emergence of new SARS-CoV-2 strains capable of evading prior immunity. The mutation and evolution of SARS-CoV-2 have created a demand for persistent efforts in vaccine development. SARS-CoV-2 Spike protein has been the primary target for COVID-19 vaccine development, but it is also the hotspot of mutations directly involved in host susceptibility and virus immune evasion. Our ability to predict emerging mutants and select conserved epitopes is critical for the development of a broadly neutralizing therapy or a universal vaccine. In this article, we review the general paradigm of immune responses to COVID-19 vaccines, highlighting the immunological epitopes of Spike protein that are likely associated with eliciting protective immunity resulting from vaccination in humans. Specifically, we analyze the structural and evolutionary characteristics of the SARS-CoV-2 Spike protein related to immune activation and function via the TLRs, B cells, and T cells. We aim to provide a comprehensive analysis of immune epitopes of Spike protein, thereby contributing to the development of new strategies for broad neutralization or universal vaccination.

Optimized production of full-length PCV2d virus-like particles in Escherichia coli: A cost-effective and high-yield approach for potential vaccine antigen development.

Porcine circovirus type 2 (PCV2) is a globally prevalent infectious pathogen affecting swine, with its capsid protein (Cap) being the sole structural protein critical for vaccine development. Prior research has demonstrated that PCV2 Cap proteins produced in Escherichia coli (E. coli) can form virus-like particles (VLPs) in vitro, and nuclear localization signal peptides (NLS) play a pivotal role in stabilizing PCV2 VLPs. Recently, PCV2d has emerged as an important strain within the PCV2 epidemic. In this study, we systematically optimized the PCV2d Cap protein and successfully produced intact PCV2d VLPs containing NLS using E. coli. The recombinant PCV2d Cap protein was purified through affinity chromatography, yielding 7.5 mg of recombinant protein per 100 ml of bacterial culture. We augmented the conventional buffer system with various substances such as arginine, ß-mercaptoethanol, glycerol, polyethylene glycol, and glutathione to promote VLP assembly. The recombinant PCV2d Cap self-assembled into VLPs approximately 20 nm in diameter, featuring uniform distribution and exceptional stability in the optimized buffer. We developed the vaccine and immunized pigs and mice, evaluating the immunogenicity of the PCV2d VLPs vaccine by measuring PCV2-IgG, IL-4, TNF-α, and IFN-γ levels, comparing them to commercial vaccines utilizing truncated PCV2 Cap antigens. The HE staining and immunohistochemical tests confirmed that the PCV2 VLPs vaccine offered robust protection. The results revealed that animals vaccinated with the PCV2d VLPs vaccine exhibited high levels of PCV2 antibodies, with TNF-α and IFN-γ levels rapidly increasing at 14 days post-immunization, which were higher than those observed in commercially available vaccines, particularly in the mouse trial. This could be due to the fact that full-length Cap proteins can assemble into more stable PCV2d VLPs in the assembling buffer. In conclusion, our produced PCV2d VLPs vaccine elicited stronger immune responses in pigs and mice compared to commercial vaccines. The PCV2d VLPs from this study serve as an excellent candidate vaccine antigen, providing insights for PCV2d vaccine research.

CA-CAS-01-A: A Permissive Cell Line for Isolation and Live Attenuated Vaccine Development Against African Swine Fever Virus.

African swine fever virus (ASFV) is the causative agent of the highly lethal African swine fever disease that affects domestic pigs and wild boars. In spite of the rapid spread of the virus worldwide, there is no licensed vaccine available. The lack of a suitable cell line for ASFV propagation hinders the development of a safe and effective vaccine. For ASFV propagation, primary swine macrophages and monocytes have been widely studied. However, obtaining these cells can be time-consuming and expensive, making them unsuitable for mass vaccine production. The goal of this study was to validate the suitability of novel CA-CAS-01-A (CAS-01) cells, which was identified as a highly permissive cell clone for ASFV replication in the MA-104 parental cell line for live attenuated vaccine development. Through a screening experiment, maximum ASFV replication was observed in the CAS-01 cell compared to other sub-clones of MA-104 with 14.89 and log10 7.5 ± 0.15 Ct value and TCID50/ml value respectively. When CAS-01 cells are inoculated with ASFV, replication of ASFV was confirmed by Ct value for ASFV DNA, HAD50/ml assay, TCID50/ml assay, and cytopathic effects and hemadsoption were observed similar to those in primary porcine alveolar macrophages after 5th passage. Additionally, we demonstrated stable replication and adaptation of ASFV over the serial passage. These results suggest that CAS-01 cells will be a valuable and promising cell line for ASFV isolation, replication, and development of live attenuated vaccines.

O26 Polysaccharides as Key Players in Enteropathogenic E. coli Immune Evasion and Vaccine Development.

Enteropathogenic Escherichia coli (EPEC) produce a capsule of polysaccharides identical to those composing the O-antigen polysaccharide of its LPS (lipopolysaccharide) molecules. In light of this, the impact of O26 polysaccharides on the immune evasion mechanisms of capsulated O26 EPEC compared to non-capsulated enterohemorrhagic Escherichia coli (EHEC) was investigated. Our findings reveal that there was no significant difference between the levels in EPEC and EHEC of rhamnose (2.8:2.5), a molecule considered to be a PAMP (Pathogen Associated Molecular Patterns). However, the levels of glucose (10:1.69), heptose (3.6:0.89) and N-acetylglucosamine (4.5:2.10), were significantly higher in EPEC than EHEC, respectively. It was also observed that the presence of a capsule in EPEC inhibited the deposition of C3b on the bacterial surface and protected the pathogen against lysis by the complement system. In addition, the presence of a capsule also protected EPEC against phagocytosis by macrophages. However, the immune evasion provided by the capsule was overcome in the presence of anti-O26 polysaccharide antibodies, and additionally, these antibodies were able to inhibit O26 EPEC adhesion to human epithelial cells. Finally, the results indicate that O26 polysaccharides can generate an effective humoral immune response, making them promising antigens for the development of a vaccine against capsulated O26 E. coli.

Uptake pathways of cell-penetrating peptides in the context of drug delivery, gene therapy, and vaccine development.

Cell-penetrating peptides have been extensively utilized for the purpose of facilitating the intracellular delivery of cargo that is impermeable to the cell membrane. The researchers have exhibited proficient delivery capabilities for oligonucleotides, thereby establishing cell-penetrating peptides as a potent instrument in the field of gene therapy. Furthermore, they have demonstrated a high level of efficiency in delivering several additional payloads. Cell penetrating peptides (CPPs) possess the capability to efficiently transport therapeutic molecules to specific cells, hence offering potential remedies for many illnesses. Hence, their utilization is imperative for the improvement of therapeutic vaccines. In contemporary studies, a plethora of cell-penetrating peptides have been unveiled, each characterized by its own distinct structural attributes and associated mechanisms. Although it is widely acknowledged that there are multiple pathways through which particles might be internalized, a comprehensive understanding of the specific mechanisms by which these particles enter cells has to be fully elucidated. The absorption of cell-penetrating peptides can occur through either direct translocation or endocytosis. However, it is worth noting that categories of cell-penetrating peptides are not commonly linked to specific entrance mechanisms. Furthermore, research has demonstrated that cell-penetrating peptides (CPPs) possess the capacity to enhance antigen uptake by cells and facilitate the traversal of various biological barriers. The primary objective of this work is to examine the mechanisms by which cell-penetrating peptides are internalized by cells and their significance in facilitating the administration of drugs, particularly in the context of gene therapy and vaccine development. The current study investigates the immunostimulatory properties of numerous vaccine components administered using different cell-penetrating peptides (CPPs). This study encompassed a comprehensive discussion on various topics, including the uptake pathways and mechanisms of cell-penetrating peptides (CPPs), the utilization of CPPs as innovative vectors for gene therapy, the role of CPPs in vaccine development, and the potential of CPPs for antigen delivery in the context of vaccine development.

Trained immunity-inducing vaccines: Harnessing innate memory for vaccine design and delivery.

While the efficacy of many current vaccines is well-established, various factors can diminish their effectiveness, particularly in vulnerable groups. Amidst emerging pandemic threats, enhancing vaccine responses is critical. Our review synthesizes insights from immunology and epidemiology, focusing on the concept of trained immunity (TRIM) and the non-specific effects (NSEs) of vaccines that confer heterologous protection. We elucidate the mechanisms driving TRIM, emphasizing its regulation through metabolic and epigenetic reprogramming in innate immune cells. Notably, we explore the extended protective scope of vaccines like BCG and COVID-19 vaccines against unrelated infections, underscoring their role in reducing neonatal mortality and combating diseases like malaria and yellow fever. We also highlight novel strategies to boost vaccine efficacy, incorporating TRIM inducers into vaccine formulations to enhance both specific and non-specific immune responses. This approach promises significant advancements in vaccine development, aiming to improve global public health outcomes, especially for the elderly and immunocompromised populations.

SARS-CoV-2 spike-FLIPr fusion protein plus lipidated FLIPr protects against various SARS-CoV-2 variants in hamsters.

Vaccine-induced mucosal immunity and broad protective capacity against various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remain inadequate. Formyl peptide receptor-like 1 inhibitory protein (FLIPr), produced by Staphylococcus aureus, can bind to various Fcγ receptor subclasses. Recombinant lipidated FLIPr (rLF) was previously found to be an effective adjuvant. In this study, we developed a vaccine candidate, the recombinant Delta SARS-CoV-2 spike (rDS)-FLIPr fusion protein (rDS-F), which employs the property of FLIPr binding to various Fcγ receptors. Our study shows that rDS-F plus rLF promotes rDS capture by dendritic cells. Intranasal vaccination of mice with rDS-F plus rLF increases persistent systemic and mucosal antibody responses and CD4/CD8 T-cell responses. Importantly, antibodies induced by rDS-F plus rLF vaccination neutralize Delta, Wuhan, Alpha, Beta, and Omicron strains. Additionally, rDS-F plus rLF provides protective effects against various SARS-CoV-2 variants in hamsters by reducing inflammation and viral loads in the lung. Therefore, rDS-F plus rLF is a potential vaccine candidate to induce broad protective responses against various SARS-CoV-2 variants.IMPORTANCEMucosal immunity is vital for combating pathogens, especially in the context of respiratory diseases like COVID-19. Despite this, most approved vaccines are administered via injection, providing systemic but limited mucosal protection. Developing vaccines that stimulate both mucosal and systemic immunity to address future coronavirus mutations is a growing trend. However, eliciting strong mucosal immune responses without adjuvants remains a challenge. In our study, we have demonstrated that using a recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-formyl peptide receptor-like 1 inhibitory protein (FLIPr) fusion protein as an antigen, in combination with recombinant lipidated FLIPr as an effective adjuvant, induced simultaneous systemic and mucosal immune responses through intranasal immunization in mice and hamster models. This approach offered protection against various SARS-CoV-2 strains, making it a promising vaccine candidate for broad protection. This finding is pivotal for future broad-spectrum vaccine development.

Immunoinformatics-driven In silico vaccine design for Nipah virus (NPV): Integrating machine learning and computational epitope prediction.

The Nipah virus (NPV) is a highly lethal virus, known for its significant fatality rate. The virus initially originated in Malaysia in 1998 and later led to outbreaks in nearby countries such as Bangladesh, Singapore, and India. Currently, there are no specific vaccines available for this virus. The current work employed the reverse vaccinology method to conduct a comprehensive analysis of the entire proteome of the NPV virus. The aim was to identify and choose the most promising antigenic proteins that could serve as potential candidates for vaccine development. We have also designed B and T cell epitopes-based vaccine candidate using immunoinformatics approach. We have identified a total of 5 novel Cytotoxic T Lymphocytes (CTL), 5 Helper T Lymphocytes (HTL), and 6 linear B-cell potential antigenic epitopes which are novel and can be used for further vaccine development against Nipah virus. Then we performed the physicochemical properties, antigenic, immunogenic and allergenicity prediction of the designed vaccine candidate against NPV. Further, Computational analysis indicated that these epitopes possessed highly antigenic properties and were capable of interacting with immune receptors. The designed vaccine were then docked with the human immune receptors, namely TLR-2 and TLR-4 showed robust interaction with the immune receptor. Molecular dynamics simulations demonstrated robust binding and good dynamics. After numerous dosages at varied intervals, computational immune response modeling showed that the immunogenic construct might elicit a significant immune response. In conclusion, the immunogenic construct shows promise in providing protection against NPV, However, further experimental validation is required before moving to clinical trials.

NS1: a promising novel target antigen with strong immunogenicity and protective efficacy for avian flavivirus vaccine development.

Tembusu virus (TMUV), an avian pathogenic flavivirus, has emerged as a significant threat to the duck industry in Southeast Asia, causing substantial economic losses. Due to the antibody-dependent enhancement (ADE) effect of TMUV subneutralizing antibodies, there is a pressing need to further develop new TMUV vaccine target antigens that ensure both safety and efficacy. Here, the TMUV non-structural protein 1 (NS1) as a target for development of effective anti-TMUV vaccines was unveiled. The amino acid sequences of TMUV NS1 exhibit a high degree of conservation across different strains (92.63-100%). To investigate the potential of TMUV NS1 as a vaccine target, the TMUV NS1-based plasmids were constructed and identified the C-terminal 30 amino acids residues of TMUV E (EC30) as an effective signal peptide for promoting NS1 expression and secretion. Subsequently, the plasmid pVAX1-EC30-NS1 was employed to immunize ducks, resulting in specific anti-NS1 IgG responses being stimulated, while without inducing anti-TMUV neutralizing antibodies. Furthermore, the cellular immune responses triggered by the TMUV NS1 were evaluated, observing a notable increase in lymphocyte proliferation at 4 wk and 6 wk postinjection with the pVAX1-EC30-NS1. Additionally, there was a significant up-regulation of NS1-specific Il-4 and Ifnγ levels at these time points. Following this, ducks from different groups were challenged with TMUV, and remarkably, those immunized with the NS1 vaccine displayed significantly lower viral copies both at 3 d postinfection (dpi) and 7 dpi (P < 0.05) compared to ducks immunized with the control vector. Notably, the NS1 demonstrated remarkable protection against TMUV challenge without causing severe gross lesions. Collectively, these findings highlighted the impressive immunogenicity and protectivity of the TMUV NS1. Consequently, NS1 holds great promise as a novel antigen target for the development of efficient and safe TMUV vaccines.

Research Note: Overview of fowl adenovirus serotype 4: structure, pathogenicity, and progress in vaccine development.

Fowl adenovirus serotype 4 (FAdV) is highly pathogenic and lethal to chickens, especially broilers, which has emerged as one of the most important economic losses for the poultry industry in the past few years. Although inactivated vaccines have been widely used to control FAdV diseases, with the passage of time and the advancement of technology, live attenuated vaccines and subunit vaccines have also been developed, which are more attractive and effective vaccine candidates. This is an overview of avian adenoviruses, especially FAdV, which is related to the structure, pathogenicity of adenoviruses in birds, development and strategies used to make and use vaccines using different methods. As well as during this study it was determined that various vaccines against the new FAdV-4 genotype have been developed and many advances have been made in control disease However, many studies conducted in this field need extensive investigation.

Updates on respiratory syncytial virus prophylaxis: the past, present and future.

PURPOSE OF REVIEW: Human respiratory syncytial virus (RSV) causes acute respiratory infection in individuals of all age groups. It is the most common pathogen identified in infants and young children with acute lower respiratory infection. Although most infants and young children experience mild, cold-like symptoms, some infants develop severe lower respiratory tract disease such as pneumonia and bronchiolitis that may result in an emergency department visit or hospitalization. RECENT FINDINGS: In the United States, hospitalization rates have risen during the last decades, and while premature infants with chronic lung disease and congenital heart disease are at increased risk for severe presentations, the majority of hospitalizations occur in previously healthy infants. Until recently, RSV prophylaxis was only available for former preterm infants and those with certain underlying medical conditions. SUMMARY: The need for preventive interventions against RSV is crucial. This paper will provide a review of the vaccine development, the spectrum of RSV prophylaxis, current challenges associated with the cost, insurance coverage and equitable distribution of targeted therapies.

Identification of a capsular polysaccharide from Enterococcus faecium U0317 using a targeted approach to discover immunogenic carbohydrates for vaccine development.

Enterococcus faecium, a gram-positive opportunistic pathogen, has become a major concern for nosocomial infections due to its resistance to several antibiotics, including vancomycin. Finding novel alternatives for treatment prevention, such as vaccines, is therefore crucial. In this study, we used various techniques to discover a novel capsular polysaccharide. Firstly, we identified an encapsulated E. faecium strain by evaluating the opsonophagocytic activity of fifteen strains with antibodies targeting the well-known lipoteichoic acid antigen. This activity was attributed to an unknown polysaccharide. We then prepared a crude cell wall glycopolymer and fractionated it, guided by immunodot-blot analysis. The most immunoreactive fractions were used for opsonophagocytic inhibition assays. The fraction containing the inhibitory polysaccharide underwent structural characterization using NMR and chemical analyses. The elucidated structure presents a branched repeating unit, with the linear part being: →)-ß-d-Gal-(1 â†’ 4)-ß-d-Glc-(1 â†’ 4)-ß-d-Gal-(1 â†’ 4)-ß-d-GlcNAc-(1→, further decorated with a terminal α-d-Glc and a d-phosphoglycerol moiety, attached to O-2 and O-3 of the 4-linked Gal unit, respectively. This polysaccharide was conjugated to BSA and the synthetic glycoprotein used to immunize mice. The resulting sera exhibited good opsonic activity, suggesting its potential as a vaccine antigen. In conclusion, our effector-function-based approach successfully identified an immunogenic capsular polysaccharide with promising applications in immunotherapy.