Limited Efficacy of a Third COVID-19 Vaccine Dose in Immunosuppressed Pediatric Patients: Antibody Levels Remain at 895 BAU
Background
Vaccination is a critical tool for controlling infectious disease spread, as demonstrated during the COVID-19 pandemic. However, the vaccine response in pediatric patients undergoing immunosuppressive therapy is likely significantly lower compared to healthy children. Children with nephrotic syndrome (NS), inflammatory bowel disease (IBD), or hematological malignancies have weakened immune systems due to their underlying conditions or treatments. Few studies have investigated the actual immune effects of a third dose of mRNA vaccine in these patients. The medical community faces the challenge of applying adult study results directly to pediatric patients. While there is hope that additional doses will protect these immune-compromised children from infection, the lack of specific immune response data makes it difficult to establish clear vaccination guidelines.
Key Findings
The researchers enrolled pediatric patients with NS, IBD, or hematological malignancies who were receiving immunosuppressive therapy and had completed their second dose of either Moderna's mRNA-1273 or Pfizer's BNT162b2 vaccine at least 150 days prior. They administered an additional vaccine dose to a total of seven immunosuppressed pediatric patients and tracked changes in humoral and cellular immune responses before and after vaccination. These results were compared to the immune responses of 14 healthy children one month after completing their primary vaccination series.
Following the additional dose, the anti-spike IgG antibody levels increased by 1.50-fold in the immunosuppressed pediatric group. However, the cellular immune response, which indicates the activity of immune cells, only increased by 1.14-fold, representing a modest improvement. In the two children with hematological malignancies, both humoral and cellular immune responses showed an increase.
Despite these increases, the actual antibody levels in the immunosuppressed pediatric patients remained significantly lower compared to healthy children. The geometric mean concentration (GMC) of anti-spike IgG in the immunosuppressed group after the additional dose was 895.62 BAU/mL, which is only 36% of the average level of 2454.56 BAU/mL in the healthy control group. Although the small sample size prevented statistical significance, the difference between the two groups was clear. In particular, the average antibody level in the two children with hematological malignancies was only 16.26 BAU/mL, indicating minimal antibody formation. The cellular immune response also remained low in the immunosuppressed group, at 69.73 SFU (Spot Forming Unit).
Significance and Outlook
This study demonstrates that the standard additional vaccine dose alone may not provide sufficient protection for pediatric patients undergoing immunosuppressive therapy. Simply increasing the number of doses may not be enough to boost their immune response to the level of healthy children. In particular, pediatric patients with hematological malignancies show very limited antibody production even after vaccination, suggesting the need for alternative treatment strategies. More diverse approaches, such as administering monoclonal antibody therapies or introducing high-dose vaccines, should be rapidly explored.
However, it is important to note that this study was limited by its small sample size. Future large-scale, multi-center clinical trials are needed to accurately assess the vaccine efficacy in immunosuppressed children. Research is also needed to determine the duration of long-term immune response and the effectiveness against variant viruses. Public health authorities and the medical community are expected to develop new, customized vaccination guidelines for immune-compromised children based on clinical data.
BACKGROUND: Immunogenicity following an additional (third) COVID-19 vaccine dose in children receiving immunosuppressive therapy remains insufficiently characterized. METHODS: We enrolled immunosuppressed children with hematological malignancies, nephrotic syndrome (NS), or inflammatory bowel disease (IBD) who had completed a two-dose primary series of mRNA-1273 or BNT162b2 at least 150 days prior to enrollment. Humoral and cellular immune responses were assessed before and after an additional dose and compared with responses in healthy children one month after primary vaccination. RESULTS: In children receiving immunosuppressive therapy (n = 7), the additional dose resulted in a 1.50-fold increase in anti-spike IgG levels and a modest 1.14-fold increase in cellular immune responses. Children with hematological cancers (n = 2) showed increases in both humoral and cellular immune responses. Despite the additional dose, anti-spike IgG levels in the immunosuppressed group (geometric mean concentration = 895.62 BAU/mL) remained lower than those in healthy controls (2454.56 BAU/mL; n = 14), although the difference was not statistically significant, while levels in the hematological cancer group were substantially lower (16.26 BAU/mL). Cellular immune responses also remained reduced in both the immunosuppressed group (69.73 SFU/2 × 10 CONCLUSIONS: Although an additional mRNA-1273 dose was associated with increased humoral and cellular immune responses in children with hematological cancers and enhanced humoral responses in immunosuppressed children, the overall magnitude of response was limited. Immunogenicity following the additional dose was modest, and the clinical benefit of an additional dose in children with NS, IBD, or hematological cancers remains uncertain.
This study provides practical evidence for refining vaccination guidelines for immunosuppressed pediatric patients. The type of underlying disease, such as nephrotic syndrome or inflammatory bowel disease, affects vaccine immune response differently. In clinical practice, it is expected that a preventive approach of directly administering prophylactic monoclonal antibodies will be introduced for patients with extremely low antibody levels, such as children with hematological malignancies, instead of simple additional vaccinations. The pharmaceutical industry will also gain the impetus to develop highly effective vaccines or immune enhancers targeting these patients. The trend is moving away from uniform prevention strategies towards individualized vaccine guidelines that consider the specific disease characteristics and medication timing of each patient.