Biological and protective properties of immune sera directed to the influenza virus neuraminidase.

نویسندگان

  • Stefan J Halbherr
  • Thomas H Ludersdorfer
  • Meret Ricklin
  • Samira Locher
  • Marianne Berger Rentsch
  • Artur Summerfield
  • Gert Zimmer
چکیده

UNLABELLED The envelope of influenza A viruses contains two large antigens, hemagglutinin (HA) and neuraminidase (NA). Conventional influenza virus vaccines induce neutralizing antibodies that are predominantly directed to the HA globular head, a domain that is subject to extensive antigenic drift. Antibodies directed to NA are induced at much lower levels, probably as a consequence of the immunodominance of the HA antigen. Although antibodies to NA may affect virus release by inhibiting the sialidase function of the glycoprotein, the antigen has been largely neglected in past vaccine design. In this study, we characterized the protective properties of monospecific immune sera that were generated by vaccination with recombinant RNA replicon particles encoding NA. These immune sera inhibited hemagglutination in an NA subtype-specific and HA subtype-independent manner and interfered with infection of MDCK cells. In addition, they inhibited the sialidase activities of various influenza viruses of the same and even different NA subtypes. With this, the anti-NA immune sera inhibited the spread of H5N1 highly pathogenic avian influenza virus and HA/NA-pseudotyped viruses in MDCK cells in a concentration-dependent manner. When chickens were immunized with NA recombinant replicon particles and subsequently infected with low-pathogenic avian influenza virus, inflammatory serum markers were significantly reduced and virus shedding was limited or eliminated. These findings suggest that NA antibodies can inhibit virus dissemination by interfering with both virus attachment and egress. Our results underline the potential of high-quality NA antibodies for controlling influenza virus replication and place emphasis on NA as a vaccine antigen. IMPORTANCE The neuraminidase of influenza A viruses is a sialidase that acts as a receptor-destroying enzyme facilitating the release of progeny virus from infected cells. Here, we demonstrate that monospecific anti-NA immune sera inhibited not only sialidase activity, but also influenza virus hemagglutination and infection of MDCK cells, suggesting that NA antibodies can interfere with virus attachment. Inhibition of both processes, virus release and virus binding, may explain why NA antibodies efficiently blocked virus dissemination in vitro and in vivo. Anti-NA immune sera showed broader reactivity than anti-HA sera in hemagglutination inhibition tests and demonstrated cross-subtype activity in sialidase inhibition tests. These remarkable features of NA antibodies highlight the importance of the NA antigen for the development of next-generation influenza virus vaccines.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Heamagglutinin Conserved Domain (HA2) Prepared in Prokaryotic System is Immunogenic in Mice but not Protective against Lethal Influenza Challenge

Background and Aims: Influenza vaccine production process is time-consuming with little-to-no cross-protection which requires annual adjustment. The construction of a universal vaccine to deal with the pandemics and epidemics which occasionally threat human population is the aim of many researches worldwide. Today, influenza vaccines are mostly against two major antigenic proteins, hemagglutini...

متن کامل

تغییرات ژنتیکی ویروس و فرار از سامانه ایمنی، چالش‌های پیش‌رو علیه آنفلوآنزا: مقاله مروری

The spread of influenza viruses in multiple bird and mammalian species is a worldwide serious threat to human and animal populations' health and raise major concern for ongoing pandemic in humans. Direct transmission of the avian viruses which have sialic acid specific receptors similar to human influenza viruses are a warning to the emergence of a new mutant strain that is likely to share mole...

متن کامل

Baculoviral Expression of Influenza A Virus (H1N1 New Caledonia) Neuraminidase in Insect Cells

Background and Aims: Each year, the influenza virus causes moderate to severe infections with a high prevalence throughout the world. Accordingly, an influenza vaccine that ensures protection with only a single dose would be a much more cost effective approach to influenza prophylaxis. Generation of Influenza non-replicating virus-like particles (VLP) in baculoviral expression system is an attr...

متن کامل

Protective Immunity in Mice Following Immunization with the Cochleate-Based Subunit Influenza Vaccines

High morbidity and mortality of influenza virus infection makes it an important disease world-wide. Mouse is a very well-studied animal model for this disease with similar manifestation to human disease. It would be desirable to induce mucosal as well as circulating immune responses to obtain protection from infection and to decrease the spread of the virus. Cell mediated immunity (proliferativ...

متن کامل

Targets for the Induction of Protective Immunity Against Influenza A Viruses

The current pandemic caused by the new influenza A(H1N1) virus of swine origin and the current pandemic threat caused by the highly pathogenic avian influenza A viruses of the H5N1 subtype have renewed the interest in the development of vaccines that can induce broad protective immunity. Preferably, vaccines not only provide protection against the homologous strains, but also against heterologo...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Journal of virology

دوره 89 3  شماره 

صفحات  -

تاریخ انتشار 2015