No licensed Shigella vaccine is presently available globally. A double-blinded, randomized, placebo-controlled, age descending phase II clinical trial of a bivalent conjugate vaccine was studied in China. The vaccine ZF0901 consisted of O-specific polysaccharides purified and detoxified from lipopolysaccharide (LPS) of S. flexneri 2a and S. sonnei and covalently bonded to tetanus toxoid. A total of 224, 310, and 434 children, consented by parents or guardians, aged 3 to 6 and 6 to 12 months and 1 to 5 years old, respectively, were injected with half or full doses, with or without adjuvant or control Hib vaccine. There were no serious adverse reactions in all recipients of ZF0901 vaccine independent of age, dosage, number of injections, or the adjuvant status. Thirty days after the last injection, ZF0901 induced robust immune responses with significantly higher levels of type-specific serum antibodies (geometric mean concentrations (GMCs) of IgG anti-LPS) against both serotypes in all age groups compared with the pre-immune or the Hib control (p < 0.0001). Here, we demonstrated that ZF0901 bivalent Shigella conjugate vaccine is safe and immunogenic in infants and young children and is likely suitable for routine immunization.
Tuberculosis (TB) remains one of the gravest global health challenges. Mycobacterium tuberculosis (M. tuberculosis), the causative agent, employs sophisticated immune evasion and pathogenesis strategies. Its capability to thrive within immune cells and incite robust inflammatory responses prolongs infection and dissemination. Mycobacterial advanced adaptations facilitate navigation through the human immune system and present a variable antigenic profile throughout different infection stages. Investigating these strategies unfolds targeted approaches to effective vaccine development against TB. This review delves into the most advanced and exhaustive insights into the immune evasion tactics and pathogenic processes of M. tuberculosis across various infection stages. The knowledge distilled from this analysis holds the promise of guiding the creation of innovative TB vaccines and translating theoretical groundwork into practical immunological defenses.
The global burden of tuberculosis (TB), exacerbated by the rise of drug-resistant Mycobacterium tuberculosis (M. tuberculosis), underscores the need for alternative intervention strategies. One promising approach is to block the infection at its earliest stage—bacterial adhesion to host cells—thereby preventing colonization and transmission without exerting selective pressure. Adhesins, surface-exposed molecules mediating this critical interaction, have therefore emerged as attractive targets for early prevention. This review outlines the infection process driven by bacterial adhesion and describes the architecture of the M. tuberculosis outer envelope, emphasizing components that contribute to host interaction. We comprehensively summarize both non-protein and protein adhesins, detailing their host receptors, biological roles, and experimental evidence. Recent progress in the computational prediction of adhesins, particularly neural network-based tools like SPAAN, is also discussed, highlighting its potential to accelerate adhesin discovery. Additionally, we present a detailed, generalized workflow for predicting M. tuberculosis adhesins, which synthesizes current approaches and provides a comprehensive framework for future studies. Targeting bacterial adhesion presents a therapeutic strategy that interferes with the early stages of infection while minimizing the risk of developing drug resistance. Consequently, anti-adhesion strategies may serve as valuable complements to conventional therapies and support the development of next-generation TB vaccines and treatments.
Introduction: Adhesion to host cells is the first and essential step in Mycobacterium tuberculosis ( M. tuberculosis ) infection. Among adhesion molecules, the PGRS domain of PE_PGRS33 plays a critical role in invasion but is dominated by B cell epitopes and lacks sufficient T cell epitopes, restricting its capacity to induce a balanced immune response. Methods: To overcome this limitation, we employed an integrative reverse vaccinology pipeline combining computational prediction and experimental validation. Helper and cytotoxic T lymphocyte epitopes were incorporated from multiple M. tuberculosis adhesins as well as other virulence-associated proteins, and adjuvant sequences were systematically evaluated in silico. Results: Among three multi-epitope constructs, the Toll-like receptor 2 (TLR2)-agonist and pan HLA DR-binding epitope (PADRE)-adjuvanted vaccine (TLR2-vaccine) emerged as the most promising candidate. In murine models, TLR2-vaccine induced strong antigen-specific antibody and IFN-γ responses, significantly reduced bacterial loads following H37Ra challenge, and effectively prevented extrapulmonary dissemination. Discussion: These findings highlight the potential of adhesin-inclusive multi-epitope vaccines to elicit both humoral and cellular immunity and demonstrate how computational vaccinology can accelerate the development of targeted interventions against tuberculosis.
19 September 2022 in Human Vaccines & Immunotherapeutics
To evaluate the safety of the 15-valent pneumococcal conjugate vaccine (PCV15 (by LvZhu & Co. Ltd)) in healthy infants aged 2 months (minimum to 6 weeks) and 3 months old. This phase I clinical trial enrolled 80 subjects in Laishui County, Hebei Province, China. The total population was divided into 4 age groups on average: 20 adults (≥18 years) and 20 children (1–5 years) all received one vaccine dose; 20 infants (3 months) received the vaccine according to a 3-dose schedule at 0, 1, and 2 months. Twenty infants (2 months, minimum of 6 weeks old) received the vaccine according to a 3-dose schedule of 0, 2, and 4 months. The adverse events (AEs) until 30 days after each dose and serious adverse events (SAEs) until 6 months after the whole dose were reported. The solicited and unsolicited AE frequencies and laboratory indices were similar among the treatment groups. No vaccine-related SAEs were reported. Most vaccine-related adverse events consisting of systemic and local reactions were fever and pain. One hypersensitivity manifested as systemic urticaria that occurred on the third day after the second dose in the 2-month group. The 15-valent pneumococcal conjugate vaccine was generally well tolerated in infants.
3 August 2026 in Human Vaccines & Immunotherapeutics
Streptococcus pneumoniae infection can cause bacterial meningitis, bacteremia, and nonbacteremic pneumonia, which is a major global public health concern.1–3 According to the World Health Organizat...