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NA's of same serotype confer partial protection

G

Ganseerpel

Advisory Board, Senior Moderator
Sandbulte MR, Jimenez GS, Boon ACM, Smith LR, Tre. Cross-Reactive

Neuraminidase Antibodies Afford Partial Protection against H5N1 in Mice and Are Present in Unexposed Humans.

PLoS Medicine Vol. 4, No. 2, e59 doi:10.1371/journ
submited by kickingbird at Feb, 14, 2007 8:29 AM from PLoS Medicine Vol. 4, No. 2, e59 doi:10.1371/journ

Background
A pandemic H5N1 influenza outbreak would be facilitated by an absence of immunity to the avian-derived virus in the human population. Although this condition is likely in regard to hemagglutinin-mediated immunity, the neuraminidase (NA) of H5N1 viruses (avN1) and of endemic human H1N1 viruses (huN1) are classified in the same serotype. We hypothesized that an immune response to huN1 could mediate cross-protection against H5N1 influenza virus infection.

Methods and Findings
Mice were immunized against the NA of a contemporary human H1N1 strain by DNA vaccination. They were challenged with recombinant A/Puerto Rico/8/34 (PR8) viruses bearing huN1 (PR8-huN1) or avN1 (PR8-avN1) or with H5N1 virus A/Vietnam/1203/04. Additional naive mice were injected with sera from vaccinated mice prior to H5N1 challenge. Also, serum specimens from humans were analyzed for reactivity with avN1. Immunization elicited a serum IgG response to huN1 and robust protection against the homologous challenge virus. Immunized mice were partially protected from lethal challenge with H5N1 virus or recombinant PR8-avN1. Sera transferred from immunized mice to na?ve animals conferred similar protection against H5N1 mortality. Analysis of human sera showed that antibodies able to inhibit the sialidase activity of avN1 exist in some individuals.

Conclusions
These data reveal that humoral immunity elicited by huN1 can partially protect against H5N1 infection in a mammalian host. Our results suggest that a portion of the human population could have some degree of resistance to H5N1 influenza, with the possibility that this could be induced or enhanced through immunization with seasonal influenza vaccines.
 
Re: NA's of same serotype confer partial protection

Can Immunity Induced by the Human Influenza Virus N1 Neuraminidase Provide Some Protection from Avian Influenza H5N1 Viruses?

<!-- end title area --><!-- start authors -->Laura Gillim-Ross, Kanta Subbarao<SUP>*</SUP>
<!-- end authors --><!-- start affiliations -->
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Published: February 13, 2007

Abbreviations: HA, hemagglutinin; NA, neuraminidase
Laura Gillim-Ross and Kanta Subbarao are in the Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
* To whom correspondence should be addressed. E-mail: ksubbarao@niaid.nih.gov

<!-- end footnote section --><HR width="100%" noShade SIZE=1><!-- start: body -->Immunity Induced by Influenza Virus Neuraminidase

The influenza virus major surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) are the principal targets of the protective immune response. Licensed seasonal influenza virus vaccines are designed to elicit a protective immune response to the HA and NA proteins. However, only the concentration of HA protein is standardized in the currently approved inactivated seasonal influenza virus vaccines; the concentration of the NA protein is not. Hemagglutinin induces strain-specific neutralizing antibodies that prevent infection by antigenically related influenza viruses. Unlike HA-specific antibodies, NA-specific antibodies do not prevent influenza virus infection, and NA immunity is referred to as infection permissive [1]. However, humoral immunity induced by NA can markedly reduce virus replication and release, shortening the severity and duration of illness, a reasonable goal in the event of an influenza pandemic [2,3]. In mice, the induction of a relatively modest NA-specific humoral response is sufficient to inhibit virus replication after challenge with homologous influenza virus [4?6]. NA-specific immunity in mice provides significant cross-protection against replication of antigenically distinct viruses of the same subtype (drift variants) but not against different subtypes [7]. The degree of relatedness between the NA used for immunization and that of the challenge virus correlates well with the degree of cross-protection conferred by an NA-specific response.

full text:http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040091
 
Re: NA's of same serotype confer partial protection

I am not convinced of the efficacy of this policy. If partial immunity is conferred with previous infection of N1, then why aren't we seeing a huge number of patients with antibodies as evidence of infection with H5N1 who were only mildly sick, or not sick at all? Why are all the cases we know of catastrophic in their presentations? We are missing something. There should be partial immunity but for some reason we don't seem to be seeing it in the real world. The only possible explanation is even partial immunity will still make you very sick.
 
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