Biology subjects

Sanz-Munoz, I.

Publications and source records attributed to Sanz-Munoz, I..

2 recordsLinked to original sources

bioRxiv2026

Neuraminidase-Based Cross-Protective Immunity against H5N1 Influenza Viruses in Humans

Highly pathogenic avian influenza A(H5N1) virus continues to expand globally across wild birds, poultry, and multiple mammalian hosts, and the detection of genetic features associated with mammalian adaptation underscores the need to better define preexisting human immunity relevant to pandemic preparedness. Although serologic and vaccine studies have historically emphasized hemagglutinin (HA), neuraminidase (NA) is a key antigen capable of providing protective immunity. Here, we performed a retrospective analysis of NA-specific antibodies in human sera collected across ten influenza seasons spanning the pre- and post-2009 pandemic periods. A total of 749 paired human serum samples (1,498 total) were obtained prior to seasonal inactivated influenza vaccination (T1) and 28 days after vaccination (T2). NA-inhibiting antibodies were measured by enzyme-linked lectin assay (ELLA) using N1 antigens representing three genotypes (B.3.13, D1.1, and EA-2021-AB) from clade 2.3.4.4b A(H5N1) viruses. In parallel, HA-directed responses were assessed by hemagglutination inhibition (HAI). In addition, luciferase-based microneutralization assays were performed to assess the presence of neutralizing antibodies. NA-inhibiting antibodies were detectable against all three genotypes across seasons. Seasonal vaccination was associated with a modest but reproducible increase in NA-inhibiting titers, most apparent from the 2009-2010 season onward, coincident with the introduction of A(H1N1)pdm09 into seasonal vaccine formulations. In contrast, HAI activity against H5 was generally low or undetectable, despite detectable HA-reactive antibodies by ELISA. These data indicate that cross-reactive NA-specific antibodies are present in human sera and can be boosted by seasonal vaccination, supporting increased consideration of NA in influenza serosurveillance and vaccine evaluation. IMPORTANCEThe continued spread of A(H5N1) viruses and reports of mammalian adaptation markers heighten concerns about potential zoonotic transmission into humans. Most studies of human antibody responses focus on influenza HA, but NA is also an important immune target. By analyzing paired sera from humans collected over ten influenza seasons, we show that NA-inhibiting antibodies cross-reacting with multiple contemporary genotypes from clade 2.3.4.4b A(H5N1) viruses are detectable and can be modestly boosted seasonal inactivated influenza vaccination, particularly after the 2009 pandemic. These findings highlight the importance of inducing NA-specific antibodies during influenza vaccination and in including NA in surveillance and in the assessment of vaccines intended to improve preparedness for emerging influenza viruses.

immunology↗

bioRxiv2024

Are we serologically prepared against an avian influenza pandemic and could seasonal flu vaccines help us?

The current situation with H5N1 highly pathogenic avian influenza virus (HPAI) is causing a worldwide concern due to multiple outbreaks in wild birds, poultry, and mammals. Moreover, multiple zoonotic infections in humans have been reported. Importantly, HPAI H5N1 viruses with genetic markers of adaptation to mammals have been detected. Together with HPAI H5N1, avian influenza viruses H7N9 (high and low pathogenic) stand out due to their high mortality rates in humans. This raises the question of how prepared we are serologically and whether seasonal vaccines are capable of inducing protective immunity against these influenza subtypes. An observational study was conducted in which sera from people born between years 1925-1967, 1968-1977, and 1978-1997 were collected before or after 28 days or 6 months post-vaccination with an inactivated seasonal influenza vaccine. Then, haemagglutination inhibition, viral neutralization, and immunoassays were performed to assess the basal protective immunity of the population as well as the ability of seasonal influenza vaccines to induce protective responses. Our results indicate that subtype-specific serological protection against H5N1 and H7N9 in the representative Spanish population evaluated was limited or nonexistent. However, seasonal vaccination was able to increase the antibody titers to protective levels in a moderate percentage of people, probably due to cross-reactive responses. These findings demonstrate the importance of vaccination and suggest that seasonal influenza vaccines could be used as a first line of defense against an eventual pandemic caused by avian influenza viruses, to be followed immediately by the use of more specific pandemic vaccines. ImportanceInfluenza A viruses (IAV) can infect and replicate in multiple mammalian and avian species. Avian influenza virus (AIV) is a highly contagious viral disease that occurs primarily in poultry and wild water birds. Due to the lack of population immunity in humans and ongoing evolution of AIV, there is a continuing risk that new IAV could emerge and rapidly spread worldwide causing a pandemic, if the ability to transmit efficiently among humans was gained. The aim of this study is to analyze the basal protection and presence of antibodies against IAV H5N1, and H7N9 subtypes in the population from different ages. Moreover, we have evaluated the h humoral response after immunization with a seasonal influenza vaccine. This study is strategically important to evaluate the level of population immunity that is a major factor when assessing the impact that an emerging IAV strain would have, and the role of seasonal vaccines to mitigate the effects of a pandemic.

immunology↗