Emergency Medical Service Personnel Recognize Pediatric Concussions.

Concussions are a major cause of morbidity in pediatrics. Many concussions occur during activities with emergency medical service (EMS) providers present to determine if a higher level of care is needed. Data are limited on how capable these providers are.

Influenza viral neuraminidase: the forgotten antigen.

Influenza is the most common cause of vaccine-preventable morbidity and mortality despite the availability of the conventional trivalent inactivated vaccine and the live-attenuated influenza vaccine. These vaccines induce an immunity dominated by the response to hemagglutinin (HA) and are most effective when there is sufficient antigenic relatedness between the vaccine strain and the HA of the circulating wild-type virus. Vaccine strategies against influenza may benefit from inclusion of other viral antigens in addition to HA.

Recombinant influenza B virus HA and NA antigens administered in equivalent amounts are immunogenically equivalent and induce equivalent homotypic and broader heterovariant protection in mice than conventional and live influenza vaccines.

Influenza B virus is an important cause of acute upper respiratory disease in humans. Vaccination is the primary method of control of influenza related disease, yet vaccine methodology and production technology have not changed in over 40 years. In this study, we compare the efficacy of recombinant baculovirus produced protein based neuraminidase containing influenza B vaccines with conventional inactivated influenza vaccine (CIV) and live-attenuated influenza vaccine (LAIV) in a murine model.

A call to cellular & humoral arms: enlisting cognate T cell help to develop broad-spectrum vaccines against influenza A.

Influenza A is an important cause of morbidity and mortality worldwide. In the United States alone influenza kills 30,000 to 50,000 people in a non-epidemic year and significantly more in an acute epidemic.(1) An emerging pandemic influenza virus, such as H5N1, could have a devastating economic and social impact.

Changing perspective on immunization against influenza.

Current vaccination strategies against influenza rely on decades old technology of strain selection and prolonged labor-intensive, embryonated chicken-egg based production methods. Although, containing both major surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), the immunity engendered by these vaccines is dominated by the anti-HA response. Consequently, current vaccines are susceptible to failure resulting from significant antigenic drift or shift in the time elapsing from the selection of the vaccine candidate strain and wild-type virus exposure.

Variation in the divalent cation requirements of influenza A virus N1 neuraminidases.

Enzymatic kinetic parameters of influenza A virus N1 neuraminidases (NA) chromatographically purified from several vaccine candidate strains were tested. With ionic strength held constant, Ca2+ or Mg2+ increased the initial rate of enzymatic activity. The 1934 and 1943 strains had statistically significant highest initial velocities, V(max)/K(m) and V(max).

Immunization against influenza A virus: comparison of conventional inactivated, live-attenuated and recombinant baculovirus produced purified hemagglutinin and neuraminidase vaccines in a murine model system.

To simulate the 2003-2004 influenza season and compare available vaccination methods, immunologically naive mice were immunized with: influenza A virus hemagglutinin (rHA) and neuraminidase (rNA) from A/Panama/2007/99 H3N2 or A/Fujian/411/2002 H3N2 expressed by recombinant baculovirus, chromatographically purified, either as single antigens (rHA or rNA) or in combination (rHArNA); conventional inactivated monovalent (CIV) vaccines from each heterotypic strain; or a live-attenuated influenza (LAV) vaccine derived from the A/Panama/2007/99 strain. HA containing vaccines were highly immunogenic for the HA antigen, with no statistically significant differences among groups in the amount of homotypic anti-HA antibody induced. Little cross-reactive anti-HA antibody was induced by any vaccine, including LAV.

Protection of mice with recombinant influenza virus neuraminidase.

Contemporary influenza vaccines are standardized with respect to their content of hemagglutinin, the major virus antigen. Although the immunizing effect of viral neuraminidase--the less abundant of the 2 major surface glycoproteins--has been well documented in experimental animals, the importance of the purified recombinant protein has not yet been adequately assessed in animals or humans. We demonstrate that different lots of a baculovirus-derived recombinant N2 protein, in the absence of other influenza virus proteins, can induce neuraminidase-specific antibodies, reduce the replication of both homologous and heterovariant virus in mice, and suppress disease, as it is manifested by total body weight loss.

Variation in the divalent cation requirements of influenza a virus N2 neuraminidases.

Influenza virus N2 neuraminidases were chromatographically purified from several vaccine candidate strains from 1957 to 1994. Enzymatic kinetic parameters and immunogenicity were tested for each strain. For each NA tested, with ionic strength held constant, Ca(2+) or Mg(2+) increased the initial rate of enzymatic activity.

The total influenza vaccine failure of 1947 revisited: major intrasubtypic antigenic change can explain failure of vaccine in a post-World War II epidemic.

Although vaccine-induced immunity to influenza A virus is continually challenged by progressively selected mutations in the virus's major antigens (antigenic drift), virus strains within a subtype (e.g., H1N1) are antigenically cross-reactive.

Supplementation of conventional trivalent influenza vaccine with purified viral N1 and N2 neuraminidases induces a balanced immune response without antigenic competition.

Influenza viruses neuraminidase (NA) were chromatographically extracted from influenza viruses A/Nanchang/933/95 H3(NC)N2(NC) [R] and A/Johannesburg/82/96 H1(JH)N1(JH) [R] and used to supplement conventional inactivated trivalent influenza vaccine. Immunization of mice with this preparation resulted in high titers of antibodies to both hemagglutinins (HA) and neuraminidases (NA); there were no significant differences in the anti-HA antibody titers between the conventional and the supplemented vaccine preparation. Likewise, there were no significant differences in anti-NA antibody titers between the supplemented vaccine and titers from mice immunized with a neuraminidase vaccine containing a mixture of N1-NA and N2-NA.