The Unfinished Agenda: Pursuing Durable Protection Against Pneumococcal Disease in People Living with Human Immunodeficiency Virus

Mehrshad  Fekri; Atiye Sadat  Abednejad

doi:10.18502/jmb.v14i1.21102

Mehrshad Fekri Department of Biochemistry, NT.C., Islamic Azad University, Tehran, Iran.
Atiye Sadat Abednejad Department of Biomedical Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran.

DOI: https://doi.org/10.18502/jmb.v14i1.21102

Keywords: Human immunodeficiency virus, Immunocompromised, Invasive pneumococcal disease, Pneumococcal conjugate vaccine, Streptococcus pneumoniae

Abstract

Background: The syndemic of the human immunodeficiency virus and Streptococcus pneumoniae infections remains a significant global health challenge. Despite effective antiretroviral therapy, people living with the human immunodeficiency virus face a 20- to 100-fold higher risk of invasive pneumococcal disease due to persistent, multifaceted immunodeficiency affecting both innate and adaptive immunity. This includes dysfunction of alveolar macrophages and neutrophils, compromised mucosal barriers, depletion of CD4+ T-cells particularly T-follicular helper cells and B-cell dysregulation, creating a perfect storm for invasive infection. The evolution from polysaccharide to conjugate vaccines represents a major advancement. Pneumococcal conjugate vaccines, by enabling T-cell-dependent responses, generate higher-quality antibodies, robust memory B-cells, and demonstrate superior immunogenicity and effectiveness in people living with the human immunodeficiency virus compared to the 23-valent pneumococcal polysaccharide vaccine. Evidence from immunogenicity studies, observational data, and the herd effects from childhood pneumococcal conjugate vaccines programs confirms that pneumococcal conjugate vaccines significantly reduce vaccine-type pneumococcal disease. However, challenges like serotype replacement, waning immunity, suboptimal response despite antiretroviral therapy, and the aging of the people living the human immunodeficiency virus population impede optimal protection.

Conclusion: While conjugate vaccines have transformed prevention, durable protection against pneumococcal disease in people living with the human immunodeficiency virus remains an unfinished agenda. Future success hinges on developing novel vaccines (e.g., protein-based), optimizing strategies with adjuvants and boosters, defining correlates of protection, and ensuring global equity in vaccine access. A multifaceted approach combining research, clinical innovation, and public health policy is essential to significantly reduce this burden