Memory B Cells and Antibody Responses to Vaccines in Infected Children (MARVIC) With Recurrent Infections: Protocol for a Prospective Observational Study.

Background: Recurrent infections are a common concern in pediatric practice and may prompt evaluation for an underlying inborn error of immunity, particularly when infections are severe, persistent, unusual, or recurrent. Recurrent sinopulmonary infections such as pneumonia, sinusitis, and otitis media may indicate a humoral immune defect, as antibody deficiencies are among the most common inborn errors of immunity. Laboratory tests typically include measurement of serum immunoglobulins (immunoglobulin G [IgG], immunoglobulin A [IgA], and immunoglobulin M [IgM]) and IgG subclasses (IgG1, IgG2, IgG3, and IgG4), assessment of vaccine-specific antibody responses, and enumeration of B-cell subsets. Together, these tests assess the quantitative and functional components of humoral immunity. However, pediatric reference intervals for these immunological parameters have not been established in Malaysia. Objective: This study aims to characterize humoral immune parameters among Malaysian children with recurrent infections, compare these parameters with those of healthy children, and establish age-specific reference values in a healthy pediatric population. Methods: The MARVIC (Memory B Cells and Antibody Responses to Vaccines in Infected Children) study is a prospective observational comparative study incorporating a vaccine challenge follow-up in children with recurrent infections and age-matched healthy controls. Eligible participants will undergo baseline assessment of serum immunoglobulins and IgG subclass concentrations using nephelometry, B-cell subsets using flow cytometry, and vaccine-specific antibody responses using enzyme-linked immunosorbent assays. They will then receive the tetanus toxoid and 23-valent pneumococcal polysaccharide vaccines, followed by repeat blood sampling 28 to 30 days later to evaluate functional antibody responses. The co-primary outcomes are between-group differences in IgG subclass concentrations, vaccine-specific antibody responses, and B-cell subsets between children with recurrent infections and healthy controls. The secondary outcome is the establishment of age-specific reference intervals for these immunological parameters among healthy children. Results: This study was funded in December 2024, and participant recruitment and data collection are ongoing. As of May 2026, a total of 145 participants had been recruited, comprising 60 (41.4%) children with recurrent infections and 85 (58.6%) healthy controls, all of whom had completed postvaccination follow-up sampling. Data collection and analysis are expected to be completed by December 2026, with publication of the findings anticipated in May 2027. Conclusions: This study will provide a comprehensive evaluation of the humoral immune profile of Malaysian children with recurrent infections. The findings may improve the identification of clinically relevant antibody deficiencies and support the interpretation of pediatric immunological investigations in Malaysia.