Pneumococcal Vaccines: Advances, Challenges, and Future Directions

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines Against Tropical and Other Infectious Diseases".

Deadline for manuscript submissions: 15 July 2026 | Viewed by 717

Special Issue Editor


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Guest Editor
Laboratório de Biologia Molecular de Microrganismos, Universidade São Francisco, Bragança Paulista 12916-900, Brazil
Interests: Streptococcus pneumoniae; vaccines; recombinant proteins; complement system; immune response

Special Issue Information

Dear Colleagues,

Streptococcus pneumoniae is a leading cause of morbidity and mortality worldwide. The global spread of antimicrobial resistance (AMR) further complicates this issue, leading to a significant increase in treatment failures. In this context, vaccination becomes a critical tool to combat AMR and reduce disease, particularly among vulnerable groups like children and the elderly. While approved pneumococcal conjugate vaccines (PCVs) have proven highly effective, their success has been hindered by serotype replacement—a consequence of the selective pressure exerted by the vaccine on a diverse pool of existing serotypes. This phenomenon necessitates frequent updates to the vaccine to include additional serotypes. However, implementing these updated formulations in low-resource settings is often challenging, resulting in uneven vaccine distribution and contributing to the ongoing spread of disease. To address these limitations, significant research is underway to develop serotype-independent vaccines, including formulations based on well-characterized conserved protein antigens and novel candidates. This Special Issue will explore the leading candidates under investigation and provide critical analyses of preclinical and clinical findings. Key topics will encompass the following:

  • Vaccine development from early-stage discovery to Phase 3 clinical trials;
  • The application and limitations of various animal models;
  • The crucial role of novel adjuvants and delivery systems.

This collection aims to provide a comprehensive overview of the field and inform future decisions regarding the development of next-generation pneumococcal vaccines and public health strategies.

We look forward to receiving your contributions.

Prof. Dr. Michelle Darrieux
Guest Editor

Manuscript Submission Information

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Keywords

  • Streptococcus pneumoniae
  • antimicrobial resistance (AMR)
  • vaccination
  • pneumococcal conjugate vaccines (PCVs)
  • serotype replacement
  • serotype-independent vaccines
  • protein antigens
  • reverse vaccinology
  • clinical trials
  • vaccine adjuvants

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Published Papers (1 paper)

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Review

38 pages, 613 KB  
Review
The Case for Pneumococcal Surface Protein A (PspA): A Comprehensive Review of a Leading Candidate in Pneumococcal Vaccine Research
by Bárbara Milani, Nauany Reis Zordan, Rodrigo Hipolito Penha, Thaisy Pacheco, Lucio Fábio Caldas Ferraz, Thaís Manzano Parisotto, Thiago Rojas Converso and Michelle Darrieux
Vaccines 2026, 14(5), 374; https://doi.org/10.3390/vaccines14050374 - 23 Apr 2026
Viewed by 366
Abstract
Streptococcus pneumoniae remains a leading cause of morbidity and mortality worldwide, with current polysaccharide-based vaccines offering limited serotype coverage, high production costs, and reduced efficacy in vulnerable populations. These limitations have prompted the search for conserved pneumococcal proteins as universal vaccine candidates. Among [...] Read more.
Streptococcus pneumoniae remains a leading cause of morbidity and mortality worldwide, with current polysaccharide-based vaccines offering limited serotype coverage, high production costs, and reduced efficacy in vulnerable populations. These limitations have prompted the search for conserved pneumococcal proteins as universal vaccine candidates. Among them, pneumococcal surface protein A (PspA) stands out as a major virulence factor, present in virtually all clinically relevant strains, and capable of interfering with complement activation, opsonophagocytosis, and host defense mechanisms. Over three decades of research have demonstrated PspA’s strong immunogenicity, protective efficacy in multiple animal models, and safety in early-phase clinical trials. Here, we critically review advances in PspA-based vaccine development, including recombinant protein fragments, fusion constructs, nanoparticle formulations, and live-vector platforms. We highlight the structural and immunological determinants underlying its protective potential, while discussing major challenges such as antigenic variability and cross-reactivity across pneumococcal strains expressing distinct PspA clades. By integrating recent experimental and translational findings, this review outlines the opportunities and obstacles for the implementation of serotype-independent PspA-based vaccines. Full article
(This article belongs to the Special Issue Pneumococcal Vaccines: Advances, Challenges, and Future Directions)
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