Abstract
Clinically used human vaccination aims to induce specific antibodies that can guarantee long-term protection against a pathogen. The reasons that other immune components often fail to induce protective immunity are still debated. Recently we found that enforced viral replication in secondary lymphoid organs is essential for immune activation. In this study we used the lymphocytic choriomeningitis virus (LCMV) to determine whether enforced virus replication occurs in the presence of virus-specific antibodies or virus-specific CD8+ T cells. We found that after systemic recall infection with LCMV-WE the presence of virus-specific antibodies allowed intracellular replication of virus in the marginal zone of spleen. In contrast, specific antibodies limited viral replication in liver, lung, and kidney. Upon recall infection with the persistent virus strain LCMV-Docile, viral replication in spleen was essential for the priming of CD8+ T cells and for viral control. In contrast to specific antibodies, memory CD8+ T cells inhibited viral replication in marginal zone but failed to protect mice from persistent viral infection. We conclude that virus-specific antibodies limit viral infection in peripheral organs but still allow replication of LCMV in the marginal zone, a mechanism that allows immune boosting during recall infection and thereby guarantees control of persistent virus.
Highlights
Detail why several vaccines produce protective antibodies but vaccines against HIV and hepatitis C virus (HCV) could not do so far
Histologic examination of the spleen on day 3 after infection with 2 × 104 plaque-forming units (PFU) of the acute strain Lymphocytic choriomeningitis virus (LCMV)-WE detected staining of LCMV along the marginal zone (Fig. 1A)
We conclude that enforced viral replication leads to the priming of CD8+ T cells, which are necessary for early viral control, whereas B cells are most likely needed for long-term protection against LCMV16,17
Summary
Detail why several vaccines produce protective antibodies but vaccines against HIV and HCV could not do so far. Enforced viral replication in the spleen is essential for activating the innate and adaptive immune systems[15] It is still unknown whether enforced viral replication occurs after vaccination or after secondary infection and whether such replication is involved in immune boosting. In the study reported here we found that, after systemic recall, infection-specific antibodies allow intracellular replication of the virus in the marginal zone of the spleen but limit the replication of infectious virus in liver, lungs, and kidneys. Upon recall infection with the persistent virus strain LCMV-Docile, spleen-specific viral replication is associated with sufficient priming of CD8+ T cells and with viral control. In contrast to specific antibodies, memory CD8+ T cells inhibit viral replication in the marginal zone fail to protect mice against persistent infection
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