Immune Responses Increased After a Third COVID-19 Vaccine Dose in Children Receiving Immunosuppressive Treatment, but Clinical Benefit Remains Uncertain
Background
Antibody responses increased after a third COVID-19 vaccine dose in children receiving immunosuppressive treatment, but the magnitude of the overall immune response was limited and the actual clinical benefit remains uncertain, a study found. The researchers assessed antibody and cellular immune responses. These findings should be distinguished from evidence demonstrating protection against infection or severe disease.
The immunogenicity of additional doses—that is, their ability to elicit an immune response—had not been fully characterized in children receiving immunosuppressive treatment for nephrotic syndrome (NS), inflammatory bowel disease (IBD), or hematologic malignancies. This study examined how immune responses changed after an additional dose in children who had completed a primary series of messenger RNA (mRNA) vaccines.
Key findings
Participants were children who had completed a two-dose primary series with mRNA-1273 or BNT162b2 at least 150 days before enrollment. They received an additional dose of mRNA-1273. The researchers measured humoral and cellular immune responses in the patient group before and after the additional dose and compared them with measurements from 14 healthy children taken one month after completion of their primary series. The groups were compared at different vaccination stages, and the abstract did not specify the exact timing of measurements after the additional dose in the patient group.
Among the seven children reported in the abstract as the immunosuppressive treatment group, anti-spike immunoglobulin G (IgG) concentrations increased to 1.50 times their pre-dose level, while cellular immune responses increased to 1.14 times their pre-dose level. Humoral and cellular responses also increased in two children with hematologic malignancies, whose results were reported separately. The abstract alone does not make clear whether these two children were included among the seven reported earlier.
After the additional dose, the geometric mean concentration of anti-spike IgG in the immunosuppressive treatment group was 895.62 BAU/mL, numerically below the 2454.56 BAU/mL in healthy controls. BAU/mL is a unit of binding antibody concentration. The difference between the groups was not statistically significant; sample size alone cannot be assumed to explain this lack of statistical significance. The anti-spike IgG concentration reported for the hematologic malignancy group was 16.26 BAU/mL.
Cellular immune responses were also numerically lower than in healthy controls. Spot-forming units (SFU) per 200,000 peripheral blood mononuclear cells (PBMCs) were 69.73 in the immunosuppressive treatment group, 17.89 in the hematologic malignancy group, and 112.26 in healthy controls. The provided abstract did not report the statistical significance of this comparison.
Neutralizing antibody titers against the BA.2 variant increased to 2.08 times the pre-dose level in the immunosuppressive treatment group and 18.12 times the pre-dose level in the hematologic malignancy group. Binding antibody concentration and neutralizing antibody titer are different measures. This is why the low binding antibody concentration in the hematologic malignancy group alone does not establish that there was no immune response. The abstract did not provide absolute neutralizing antibody titers, so the post-dose level of protection cannot be assessed from the fold increases alone.
Meaning and outlook
Immune markers increased after the additional dose, but the researchers characterized the magnitude of the overall immune response as limited. They concluded that the clinical benefit of an additional dose remains uncertain for children with nephrotic syndrome, inflammatory bowel disease, or hematologic malignancies. The study did not establish that additional doses cannot prevent infection or recommend replacing them with other preventive measures.
The study was small, and the provided abstract did not report the exact timing of blood collection after the additional dose in the patient group, the duration of immune responses, or outcomes such as infection, hospitalization, or severe disease. Establishing differences by disease or changing vaccination strategies requires follow-up evidence assessing both immune markers and actual clinical outcomes.
Source: Abstract of a paper in Pediatrics and Neonatology indexed in Europe PMC.
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.
When counseling about additional doses for children receiving immunosuppressive treatment, this study can help distinguish changes in antibody measurements from actual protection against infection. For example, the hematologic malignancy group had a low binding antibody concentration, while BA.2 neutralizing antibody titers increased. This illustrates why a single measure cannot adequately characterize the overall vaccine response. However, a large fold increase in neutralizing antibody titers does not establish that sufficient protection was achieved. Follow-up studies evaluating vaccination strategies should specify the diseases, treatment conditions, and timing of post-dose measurements, and should also assess infection and severe disease outcomes. This abstract alone does not support replacing vaccination with monoclonal antibodies or introducing high-dose vaccines.