The germinal center (GC) response plays a crucial role in generating high-affinity antibody producing plasma cells and memory B cells, which is essential for long-term immunity and effective vaccination. However, enhancing the antibody affinity poses a significant challenge. In this study, we discovered that ‘NewSTAR2’, i.e. targeting TNFRII by a TNFRII-specific TNF fusion protein, could increase the efficacy of keyhole limpet hemocyanin (NP-KLH) immunization. NewSTAR2 significantly enhanced the frequencies of follicular helper T cells and GC-B cells during NP-KLH immunization in vivo. Moreover, it augmented the total amount of immunoglobulins in the serum and improved the affinity of anti-NP-specific antibodies. Additionally, NewSTAR2 dramatically increased the expression of CD80 and CD86 on B cells, along with promoting the proliferation and the frequency of GC-B cells in vitro. Taking together, these findings suggest that NewSTAR2 could be employed as an adjuvant to promote vaccine effectiveness.