RESUMEN
Influenza A viruses pose a significant threat to global health, impacting both humans and animals. Zoonotic transmission, particularly from swine and avian species, is the primary source of human influenza outbreaks. Notably, avian influenza viruses of the H5N1, H7N9, and H9N2 subtypes are of pandemic concern through their global spread and sporadic human infections. Preventing and controlling these viruses is critical due to their high threat level. Vaccination remains the most effective strategy for influenza prevention and control in humans, despite varying vaccine efficacy across strains. This review focuses specifically on pandemic preparedness for avian influenza viruses. We delve into vaccines tested in animal models and summarize clinical trials conducted on H5N1, H7N9, and H9N2 vaccines in humans.
Asunto(s)
Aves , Vacunas contra la Influenza , Gripe Aviar , Gripe Humana , Pandemias , Animales , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Humanos , Gripe Humana/prevención & control , Gripe Humana/epidemiología , Gripe Humana/inmunología , Gripe Aviar/prevención & control , Gripe Aviar/epidemiología , Pandemias/prevención & control , Desarrollo de Vacunas , Subtipo H7N9 del Virus de la Influenza A/inmunología , Subtipo H9N2 del Virus de la Influenza A/inmunología , Subtipo H5N1 del Virus de la Influenza A/inmunología , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Vacunación , Preparación para una PandemiaRESUMEN
The hemagglutinin (HA) stem region is a major target of universal influenza vaccine efforts owing to the presence of highly conserved epitopes across multiple influenza A virus (IAV) strains and subtypes. To explore the potential impact of vaccine-induced immunity targeting the HA stem, we examined the fitness effects of viral escape from stem-binding broadly neutralizing antibodies (stem-bnAbs). Recombinant viruses containing each individual antibody escape substitution showed diminished replication compared to wild-type virus, indicating that stem-bnAb escape incurred fitness costs. A second-site mutation in the HA head domain (N129D; H1 numbering) reduced the fitness effects observed in primary cell cultures and likely enabled the selection of escape mutations. Functionally, this putative permissive mutation increased HA avidity for its receptor. These results suggest a mechanism of epistasis in IAV, wherein modulating the efficiency of attachment eases evolutionary constraints imposed by the requirement for membrane fusion. Taken together, the data indicate that viral escape from stem-bnAbs is costly but highlights the potential for epistatic interactions to enable evolution within the functionally constrained HA stem domain.
Asunto(s)
Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Anticuerpos ampliamente neutralizantes/genética , Epistasis Genética , Glicoproteínas Hemaglutininas del Virus de la Influenza , Vacunas contra la Influenza/genética , Hemaglutininas , Gripe Humana/genética , Gripe Humana/prevención & controlRESUMEN
Influenza A and B viruses are among the most prominent human respiratory pathogens. About 3-5 million severe cases of influenza are associated with 300 000-650 000 deaths per year globally. Antivirals effective at reducing morbidity and mortality are part of the first line of defense against influenza. FDA-approved antiviral drugs currently include adamantanes (rimantadine and amantadine), neuraminidase inhibitors (NAI; peramivir, zanamivir, and oseltamivir), and the PA endonuclease inhibitor (baloxavir). Mutations associated with antiviral resistance are common and highlight the need for further improvement and development of novel anti-influenza drugs. A summary is provided for the current knowledge of the approved influenza antivirals and antivirals strategies under evaluation in clinical trials. Preclinical evaluations of novel compounds effective against influenza in different animal models are also discussed.
