Effector-independent in vivo Activity of a Strong Influenza B Neuraminidase Widely Neutralizing Antibody

Laura Righetto^*
*Correspondence: Laura Righetto, Department of Biology and Biotechnology, University of Padua, via Ugo Bassi, 58/B, 35131 Padua, Italy, Email:

Keywords

Influenza B • Neuraminidase • Neutralizing antibody • Antiviral therapy

Introduction

Influenza B virus (IBV) is a prominent cause of seasonal flu epidemics, contributing to significant morbidity and mortality worldwide. Despite the availability of vaccines and antiviral drugs, the virus's ability to undergo antigenic drift and shift necessitates continuous development of novel therapeutic strategies. Among the promising avenues is the utilization of broadly neutralizing antibodies (bnAbs) that target conserved viral components, offering potential cross-protection against diverse strains [1].

Neuraminidase (NA), a surface glycoprotein critical for the viral lifecycle, is a prime target for these bnAbs. NA facilitates the release of new virions from infected cells, thus spreading the infection. Antibodies that inhibit NA activity can effectively neutralize the virus by preventing this release. However, traditional Antibody-Dependent Cellular Cytotoxicity (ADCC) and Complement-Dependent Cytotoxicity (CDC) mechanisms may not fully account for the observed efficacy of certain anti-NA antibodies. This article investigates the effector-independent activity of a potent anti-NA bnAb, examining its mechanism and potential implications for influenza B treatment [2].

Literature Review

Previous studies have extensively explored the role of Neuraminidase Inhibitors (NAIs) in treating influenza infections. Oseltamivir and zanamivir, two widely used NAIs, have demonstrated efficacy in reducing the severity and duration of influenza symptoms. However, the emergence of drug-resistant strains underscores the need for alternative therapeutic approaches. Research on NA-targeting antibodies has highlighted their potential in providing broader and more robust protection compared to NAIs. Studies demonstrated that anti-NA antibodies could confer protection against diverse influenza strains in animal models. These antibodies, by binding to conserved NA epitopes, inhibit enzymatic activity and viral release, thereby neutralizing the virus [3].

Despite these promising findings, the precise mechanisms underlying the efficacy of anti-NA antibodies remain incompletely understood. Traditional effector functions, such as ADCC and CDC, have been proposed as major contributors to antibody-mediated protection. However, recent evidence suggests that certain anti-NA antibodies can neutralize influenza viruses in vivo without relying on these effector functions. This effector-independent activity warrants further investigation to elucidate its underlying mechanisms and potential therapeutic implications. The effector-independent activity of anti-NA bnAbs represents a paradigm shift in our understanding of antibody-mediated viral neutralization. Unlike conventional antibodies that rely on recruiting immune effector functions, these bnAbs can directly inhibit viral replication by blocking NA activity. This mode of action is particularly advantageous in scenarios where immune effector functions may be compromised or ineffective, such as in immunocompromised individuals [4].

Discussion

The antibody in focus, referred to as NA-WNA, exhibits robust in vivo activity against influenza B virus. Studies have demonstrated its ability to significantly reduce viral titers and ameliorate disease symptoms in animal models. NA-WNA binds to a conserved epitope on the NA surface, thereby inhibiting its sialidase activity. This inhibition prevents the release of progeny virions from infected cells, effectively halting the spread of infection. One of the critical advantages of NA-WNA is its broad reactivity across different influenza B strains. This broad reactivity is attributed to the conserved nature of the target epitope, which is less prone to antigenic variation compared to other viral components. Consequently, NA-WNA offers potential cross-protection against a wide range of circulating and emerging influenza B strains, addressing a significant limitation of current vaccines and antiviral drugs [5].

The effector-independent mechanism of NA-WNA also reduces the risk of adverse reactions associated with excessive immune activation. Traditional antibody therapies that rely on ADCC and CDC can trigger inflammation and tissue damage, particularly in individuals with pre-existing conditions. By circumventing these effector functions, NA-WNA minimizes the likelihood of such adverse effects, making it a safer therapeutic option. However, the development and deployment of NA-WNA face several challenges. The large-scale production of monoclonal antibodies is complex and costly, posing logistical and economic barriers. Additionally, the potential for the emergence of NA escape mutants, although theoretically lower due to the conserved nature of the target epitope, remains a concern. Continuous surveillance and development of combination therapies may be necessary to mitigate this risk [6].

Conclusion

The effector-independent in vivo activity of a strong influenza B neuraminidase widely neutralizing antibody represents a significant advancement in influenza therapeutics. By directly inhibiting NA activity, this bnAb offers broad and robust protection against diverse influenza B strains, addressing key limitations of current vaccines and antiviral drugs. Its effector-independent mechanism reduces the risk of adverse reactions, making it a safer option for vulnerable populations. However, challenges related to production, cost, and potential viral escape must be addressed to fully realize the therapeutic potential of NA-WNA. Further research and clinical trials are essential to validate its efficacy and safety in humans. Nonetheless, the promising findings presented in this article underscore the potential of NA-WNA as a novel and effective tool in the fight against influenza B.

Acknowledgement

None.

Conflict of Interest

None.

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