Enhancing Vaccine Half-life as a Novel Strategy for Improving Immune Response Durability of Subunit Vaccines
Zhaoling Shen, Cheng Li, Wenping Song, Litong Liu, Yu Kong, Ailing Huang, Qingui Bao, Tianlei Ying, Yanling Wu.
Abstract
Vaccines are widely regarded as one of the most effective strategies for combating infectious diseases. However, significant challenges remain, such as insufficient antibody levels, limited protection against rapidly evolving variants, and poor immune durability, particularly in subunit vaccines, likely due to their short in vivo exposure. Recent advances in extending the half-life of protein therapeutics have shown promise in improving drug efficacy, yet whether increasing in vivo persistence can enhance the efficacy of subunit vaccines remains underexplored.
Introduction
Vaccines are critical for combating infectious diseases and offer protection against a wide range of pathogens. Although multiple vaccines have been developed, several challenges remain, including insufficient antibody levels, limited breadth of protection against rapidly evolving variants and poor durability of immunity. Generally, critical proteins displayed on the viral surface, which are involved in virus entry, serve as potent candidates for subunit vaccine design because they can induce specific neutralizing antibodies that effectively prevent viral invasion.
Materials and Methods:
This designed protein sequence is further fused at its N-terminus in a tandem manner with the sequences of a heavy chain signal peptide of the antibody to guarantee protein secretion, a Trx tag to help protein folding, a 6xHis tag to facilitate protein purification, and an enterokinase (EK) cleavage site for tag removal. The gene sequence described above was first amplified via PCR and then incorporated into the pcDNA3.1 vector via the BmtI and HindIII restriction sites.
Discussion
Compared with other types of vaccines, such as inactivated or live-attenuated vaccines, recombinant protein vaccines offer significant advantages, including high safety due to the absence of viral genome integration and cost-effectiveness, making them strong candidates for widespread use. This study highlights the design and development of a protein-based vaccine with enhanced in vivo persistence, demonstrating its ability to elicit robust and enduring neutralizing antibody responses.
Acknowledgments
We thank the Center of Cryo-Electron Microscopy, Fudan University, for support with cryo-EM data collection. We thank Dexin Xu from the Key Laboratory of Medical Molecular Virology, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, for technical support.
Citation: Shen Z, Li C, Song W, Liu L, Kong Y, Huang A, et al. (2025) Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines. PLoS Pathog 21(1): e1012845. https://doi.org/10.1371/journal.ppat.1012845
Editor: Haitao Hu, The University of Texas Medical Branch at Galveston, UNITED STATES OF AMERICA
Received: September 25, 2024; Accepted: December 17, 2024; Published: January 8, 2025.
Copyright: © 2025 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All data are in the manuscript and/or supporting information files.
Funding: This work was supported by grants from the Ministry of Science and Technology of China (2019YFA0904400 to T.Y.), the National Natural Science Foundation of China (32270984 to Y.W.), the Science and Technology Commission of Shanghai Municipality (23XD1400800 to T.Y.), and the Shanghai Municipal Health Commission (GWVI-11.2-YQ46 to Y.W.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
