Abstract
Influenza causes millions of cases of hospitalizations annually and remains a public health concern on a global scale. Vaccines are developed and have proven to be the most effective countermeasures against influenza infection. Their efficacy has been largely evaluated by hemagglutinin inhibition (HI) titers exhibited by vaccine-induced neutralizing antibodies, which correlate fairly well with vaccine-conferred protection. Contrarily, non-neutralizing antibodies and their therapeutic potential are less well defined, yet, recent advances in anti-influenza antibody research indicate that non-neutralizing Fc-effector activities, especially antibody-dependent cellular cytotoxicity (ADCC), also serve as a critical mechanism in antibody-mediated anti-influenza host response. Monoclonal antibodies (mAbs) with Fc-effector activities have the potential for prophylactic and therapeutic treatment of influenza infection. Inducing mAbs mediated Fc-effector functions could be a complementary or alternative approach to the existing neutralizing antibody-based prevention and therapy. This review mainly discusses recent advances in Fc-effector functions, especially ADCC and their potential role in influenza countermeasures. Considering the complexity of anti-influenza approaches, future vaccines may need a cocktail of immunogens in order to elicit antibodies with broad-spectrum protection via multiple protective mechanisms.
Highlights
Influenza viruses cause severe respiratory illness, leading to 290,000–650,000 deaths annually worldwide as estimated by the World Health Organization (WHO) [1]
FcγRIIIa is used as effector cells and expresses firefly luciferase when activated by nuclear factor of activated T cells (NFAT)-response element during the time when FcγRs are bound by fragment crystallizable (Fc) portion of the antibody
The protective efficacy of influenza vaccines largely depends on the stimulation of neutralizing antibodies
Summary
Influenza viruses cause severe respiratory illness, leading to 290,000–650,000 deaths annually worldwide as estimated by the World Health Organization (WHO) [1]. Through binding to viral surface proteins HA inactivated and recombinant HA vaccines are the three types of licensed seasonal influenza vaccines and NA, antibodies can block the essential steps in the virus replication cycle, thereby limiting the [9]. These vaccines conferred considerable protection in combating influenza by inducing antibodies spread infection. These facilitate the elimination of influenza virus-infected cells [28] This Fc-receptor binding activity was confirmed to confer protection in animal models in the absence of neutralizing antibodies [29]. Only one HIV vaccine, RV144, shows modest efficacy (31% efficacy) and this efficacy is not associated with neutralizing antibodies but with potent ADCC-Abs [54,55,56,57,58]
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