Vaccines preventing neonatal sepsis: focus on Group B <i>Streptococcus</i> , <i>Klebsiella pneumoniae</i> and <i>Escherichia coli</i> to combat rising antimicrobial resistance

Introduction Neonatal sepsis, a systemic infection occurring in infants within their first 28 days of life, is a leading cause of mortality globally. The burden is especially severe in low- and middle-income countries (LMICs), where incidence and mortality rates are higher than in high-resource settings. Antimicrobial resistance, driven by multidrug-resistant pathogens prevalent in LMICs, further complicates its effective management. Vaccination offers a promising strategy to prevent infections caused by common neonatal sepsis pathogens, potentially reducing sepsis incidence and mitigating resistance.Area covered This review examines the burden of bacterial pathogens, specifically Group B Streptococcus (GBS), Klebsiella pneumoniae, and Escherichia coli, responsible for neonatal sepsis, drawing from a comprehensive literature search focusing on the last ten years across major databases. It provides an overview of vaccine candidates in clinical development, highlights innovative approaches in preclinical research, and discusses the key challenges associated with vaccine strategies preventing neonatal sepsis.Expert opinion Given the multivalency of vaccines for neonatal sepsis, innovative technologies are under investigation. Defining correlate of protections has been critical for GBS vaccine development, and may pave the way for vaccines against K. pneumoniae and E. coli. Novel regulatory and clinical strategies, including disease-based rather than pathogen specific approaches, should be explored.