Jul 2026· SAR Journal of Pathology and Microbiology· Vol 7, pp. 210-220· 0 citations
TL;DR
The review emphasizes the necessity of global surveillance programs to monitor viral evolution in real-time and calls for a collaborative, interdisciplinary approach to create more robust and future-proof vaccination strategies, thereby mitigating the risk of vaccine-driven viral and ensuring long term efficacy.
Abstract
This review examines the critical challenge of evolving animal virus resistance to vaccines, a phenomenon threatening veterinary medicine, global food security, and public health. While effective for controlling bacterial diseases, vaccination against rapidly mutating RNA viruses often imposes strong selective pressures, driving the emergence of antigenic variants that evade host immunity. These vaccines escape mutants, evidenced in viruses like canine parvovirus (CPV), avian influenza (AIV), and foot-and-mouth disease (FMD), lead to outbreaks in vaccinated populations and complicate disease management. The paper elucidates the mechanisms behind this resistance, primarily genetic mutations in antigenic sites and sophisticated immune evasion strategies, which enable viruses to circumvent neutralization by vaccine-induced antibodies. It critically evaluates the limitations of current vaccine technologies, including inactivated, live-attenuated, and subunit vaccines, noting that imperfect immunity can inadvertently promote the selection of resistant strains. To address this ongoing evolutionary arms race, the authors advocate for a paradigm shift in vaccine design. They propose leveraging advanced technologies such as viral vector platforms, structural biology, and predictive modeling to develop next-generation vaccines targeting conserved epitopes. Furthermore, the review emphasizes the necessity of global surveillance programs to monitor viral evolution in real-time and calls for a collaborative, interdisciplinary approach to create more robust and future-proof vaccination strategies, thereby mitigating the risk of vaccine-driven viral and ensuring long term efficacy.
Despite the presence of licensed vaccines and therapeutics, influenza viruses remain a major public health concern, as they cause seasonal respiratory infections and pose a pandemic threat through the emergence of zoonotic strains. Although neutralizing antibodies elicited by seasonal vaccination constitute a primary defense against infection, their protective capacity is often limited because they frequently target the epitopes that are highly susceptible to structural changes through viral evolution. To overcome this challenge, broadly protective antibodies have been intensively investigated in both humans and animal models. These antibodies recognize conserved epitopes and confer protection through multiple mechanisms beyond conventional neutralization. Recent advances in antibody discovery technologies and structural biology have enabled high‐resolution mapping of conserved epitopes and the on‐target antibodies that bind them. Furthermore, although broadly protective antibodies are typically elicited only at low frequencies following standard vaccination, several settings have been reported in which their induction is enhanced. Those findings increase the feasibility of epitope‐focused vaccine strategies for enhancing the breadth and durability of antibody responses. In this review, we summarize current knowledge of broadly protective flu antibodies and discuss how mechanistic and structural insights can guide the development of next‐generation influenza vaccines that offer broad‐spectrum protection against antigenically diverse viruses.
Human norovirus (HuNoV) is a leading cause of acute viral gastroenteritis worldwide and represents a major unmet challenge in antiviral drug and vaccine development. HuNoV is a non-enveloped, positive-sense RNA virus characterized by extensive genetic diversity and rapid evolution, which contribute to recurrent outbreaks in the absence of effective licensed therapeutics. Despite substantial progress in understanding HuNoV molecular biology, effective antiviral strategies remain limited, in part due to historical limitations in experimental model systems and the virus’s ability to evade host antiviral responses. Recent advances in HuNoV in vitro culture systems, particularly human intestinal enteroids, and inhibitor screening platforms have improved the identification of antiviral candidates, while parallel efforts in vaccine development have yielded immunogenicity data in preclinical and early-stage clinical studies. However, significant challenges persist, including antigenic diversity, strain-specific immunity, and limited correlates of protection. This review provides a critical analysis of the molecular mechanisms governing HuNoV infection, immune evasion, and replication, with a focused emphasis on key antiviral targets, inhibitory strategies, and therapeutic development. Moreover, this review outlines key limitations and future directions for the development of effective therapeutic and preventive measures against HuNoV infection.
Sadia Islam, Sabbir Zia, Simonto Mirza et al.· Therapeutic Advances in Infe...· 0 citations
ABSTRACT The H9N2 avian influenza virus (AIV) has caused substantial economic losses to the global poultry industry and poses a zoonotic threat to humans. Vaccination constitutes a pivotal strategy for the prevention and control of H9N2 AIVs. However, the ongoing antigenic evolution of the viruses pose a persistent challenge to the protective efficacy of existing vaccines. Therefore, the development of a broadly protective H9N2 influenza vaccine capable of eliciting cross-reactive immune responses is crucial for mitigating both the disease burden and the risk of pandemics. Here, we developed a bivalent chimeric inactivated vaccine, designated cHANA, by combining two individually rescued chimeric inactivated viruses, cHANA1 and cHANA2. Each recombinant virus carries one set of Epigraph-designed HA and NA immunogens, and the two sets were computationally optimized from global H9N2 HA and NA sequence datasets to complement each other in epitope coverage across the H9N2 viral population. Compared to the WHO-recommended candidate vaccine virus (CVV), AL/39, cHANA elicited more potent cross-reactive antibody responses and T cell immunity in mice. Furthermore, it elicited effective cross-protection against lethal challenge with heterologous H9N2 virus and significantly reduced pulmonary viral loads of mice. By conferring broad protective immunity, this vaccine represents a promising universal vaccine candidate for controlling H9N2 outbreaks.
Mengchan Hao, Yiwei Guan, Meng Xu et al.· Emerging Microbes and Infect...· 0 citations
Swine Group A rotavirus is one of the primary intestinal pathogens causing severe diarrhea in newborn piglets, with high incidence and mortality resulting in substantial economic losses to the global swine industry. Vaccination, alongside rigorous biosecurity measures, remains the core strategy for controlling porcine Group A rotavirus infection; however, continuous genetic variation via genomic reassortment, point mutations, and diverse G/P genotype combinations drives the constant emergence of new circulating strains that may evade immune protection from existing vaccines. These genetic changes may also give rise to highly pathogenic variants, increasing large-scale outbreak risk. Therefore, developing vaccines that provide stable, broad cross-protection against viral strain diversity is particularly critical. Vaccine adjuvants play a vital role in enhancing and modulating immune responses, broadening protection spectra, and reducing the antigen dose required for protection especially valuable when facing rapidly changing genotypes or limited vaccine antigen supplies. In recent years, advances in adjuvant design and formulation strategies have clearly improved the immunogenicity and duration of protection of swine Group A rotavirus vaccines, as evidenced by significantly reduced diarrhea incidence and viral shedding intensity in vaccinated piglets. Building on an overview of the current status, advantages, and challenges of different porcine Group A rotavirus vaccine types, this review focuses on the mechanisms of action, application advantages, existing limitations, and methodological strategies of adjuvants. It further analyzes the potential contribution of adjuvant strategies to developing a universal porcine rotavirus vaccine capable of broad, long-lasting cross-protection. Finally, this review identifies key unresolved scientific questions and critical knowledge gaps in the field, with the aim of guiding future research priorities.
Zhang Zhen, Ma Baihe, Hongmiao Zhou et al.· Frontiers in Veterinary Scie...· 0 citations
Foot‐and‐mouth disease virus (FMDV) escapes host immune surveillance via adaptive evolution driven by vaccine‐mediated selective pressure, leading to persistent breakthrough infections in immunized animals. In this study, the dominant neutralizing epitope VP1 G–H loop (141–160 aa) was analyzed among 46 serotype O FMDV strains belonging to Southeast Asian (SEA) and Middle East–South Asian (ME‐SA) topotypes isolated during 1980–2019. The key amino acid residues at VP1 positions 142 and 153 underwent sequential stepwise evolution across three phases under natural selection. Based on the reverse genetic system of Wt, single‐site mutant (T142P, Q153P) and double‐site mutant (T142P&Q153P) strains were rescued. These mutation sites were further introduced into an efficient FMDV nanoparticle vaccine to construct four vaccine candidates. Mouse immunization verified all vaccines conferred solid protection against Wt and single‐mutant strains, yet protection efficacy was greatly impaired against the double mutant. The double‐mutant vaccine elicited high‐level neutralizing antibodies against the double‐mutant strain (T142P&Q153P) with a titer of 1:426.67, 10–20 folds higher than Wt (1:21.33), T142P (1:32), and Q153P (1:42.67) vaccines. Consistent results were also obtained in pigs immunized with commercial inactivated vaccines. Collectively, combined mutations at VP1 142 and 153 reshape viral antigenicity and act as core drivers of FMDV immune evasion. Integrating such immune escape hotspots into vaccine antigens can broaden neutralizing antibody coverage, offering an experimental basis for clarifying FMDV evolution and developing broad‐spectrum vaccines.
Nan Cao, Yamei Li, Xinghua Chen et al.· Transboundary and Emerging D...· 0 citations
This review comprehensively evaluates the rational design of classical animal herpesvirus vectors, including pseudorabies virus, herpesvirus of turkeys, and feline herpesvirus type 1, providing perspectives on how continuous biotechnological innovations will empower herpesvirus vectors to serve as formidable prophylactic tools against emerging and re-emerging infectious diseases.
Jia-Hui Guo, Chen Mei, Xin-Yao Sun et al.· Frontiers in Microbiology· 0 citations
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