B-Cell Responses to Human Bocaviruses 1-4: New Insights from a Childhood Follow-Up Study

Abstract

Human bocaviruses (HBoVs) 1-4 are recently discovered, antigenically similar parvoviruses. We examined the hypothesis that the antigenic similarity of these viruses could give rise to clinically and diagnostically important immunological interactions. IgG and IgM EIAs as well as qPCR were used to study ~2000 sera collected from infancy to early adolescence at 3-6-month intervals from 109 children whose symptoms were recorded. We found that HBoV1-4-specific seroprevalences at age 6 years were 80%, 48%, 10%, and 0%, respectively. HBoV1 infections resulted in significantly weaker IgG responses among children who had pre-existing HBoV2 IgG, and vice versa. Furthermore, we documented a complete absence of virus type-specific immune responses in six viremic children who had pre-existing IgG for another bocavirus, indicating that not all HBoV infections can be diagnosed serologically. Our results strongly indicate that interactions between consecutive HBoV infections affect HBoV immunity via a phenomenon called "original antigenic sin", cross-protection, or both; however, without evident clinical consequences but with important ramifications for the serodiagnosis of HBoV infections. Serological data is likely to underestimate human exposure to these viruses.

Fig 1. Human bocavirus 1–3 seroprevalences (dashed lines) and cumulative seroconversion rates (solid lines) in different age groups.

Fig 2. Pre-existing HBoV1 IgG reduces immune response against HBoV2 infection.

Two representative cases of PCR-verified HBoV2 infections without (child #52) or with (child #108) pre-existing HBoV1 IgG are shown. The red, blue and black data points respectively indicate whether the serum tested positive by PCR, tested negative by PCR, or was not tested by PCR. Although not shown in the graphs, both children tested negative for HBoV3- and 4-specific IgG.

Fig 3. Pre-existing HBoV2 IgG reduces immune response against HBoV1 infection.

Two illustrative cases of PCR-verified HBoV1 infections without (child #53) or with (child #122) pre-existing HBoV2 IgG are shown. The red, blue and black data points respectively indicate whether the serum tested positive by PCR, tested negative by PCR, or was not tested by PCR. The red open circle indicates a sample that was positive for HBoV1 IgM. Although not shown in the graphs, both children tested negative for HBoV3- and 4-specific IgG.