Evaluation of age-related differences in the immunogenicity of a G9 H9N2 influenza vaccine.

Avian influenza A/H9N2 viruses can infect people and are viruses considered to be a potential pandemic threat. Prior studies with an inactivated G1 clade H9N2 vaccine reported that persons born before 1968 were more likely to have an immune response than younger subjects. We performed a randomized, double-blind trial to evaluate whether immune responses following immunization with an inactivated, unadjuvanted influenza G9 H9N2 vaccine prepared from A/chicken/Hong Kong/G9/97 virus were more frequent in persons born in 1964 or earlier (44-59 years) than in those born in 1970 or later (18-38 years).

Comparison of the immunogenicity and safety of a split-virion, inactivated, trivalent influenza vaccine (Fluzone®) administered by intradermal and intramuscular route in healthy adults.

The aim of the study was to determine whether reduced doses of trivalent inactivated influenza vaccine (TIV) administered by the intradermal (ID) route generated similar immune responses to standard TIV given intramuscularly (IM) with comparable safety profiles. Recent changes in immunization recommendations have increased the number of people for whom influenza vaccination is recommended. Thus, given this increased need and intermittent vaccine shortages, means to rapidly expand the vaccine supply are needed.

A high dosage influenza vaccine induced significantly more neuraminidase antibody than standard vaccine among elderly subjects.

Antibody to the neuraminidase (NA) antigen of influenza viruses has been shown to correlate with immunity to influenza in humans and animal models. In a previous report, we showed that an inactivated influenza vaccine containing 60microg of the hemagglutinin (HA) of each strain induced significantly more serum anti-HA antibody among elderly persons than did the standard vaccine containing 15microg of the HA of each component. We developed a lectin-based assay for anti-NA antibody and used it to measure anti-NA antibody responses among subjects who had participated in that study.

A phase I evaluation of inactivated influenza A/H5N1 vaccine administered by the intradermal or the intramuscular route.

In a phase I clinical trial, one hundred healthy young adults were randomized to receive two doses 28 days apart of an inactivated, subvirion vaccine containing 15 or 45microg of influenza A/H5N1 hemagglutinin (HA) by the intramuscular (IM) route, or 3 or 9microg of H5 HA by the intradermal(ID) route. Seventy-seven subjects received a third dose. All regimens were safe and well tolerated.

Contrasting effects of type I interferon as a mucosal adjuvant for influenza vaccine in mice and humans.

To identify an adjuvant that enhances antibody responses in respiratory secretions to inactivated influenza virus vaccine (IVV), a comparison was made of responses to intranasal vaccinations of mice with IVV containing monophosphoryl lipid A (MPL), type I interferon (IFN) or cholera toxin B (CTB). Antibody in nasal secretions and lung wash fluids from mice was increased after vaccination and lung virus was significantly reduced after challenge to a similar level in each adjuvant group. Interferon was selected for a trial in humans.

Increasing doses of an inactivated influenza A/H1N1 vaccine induce increasing levels of cross-reacting antibody to subsequent, antigenically different, variants.

Immunization approaches that will broaden antibody responses to antigenically different variants of influenza viruses are needed because vaccine strains do not always match the viruses that circulate during the subsequent epidemic. Sera collected from subjects who were vaccinated with various doses of influenza A/Taiwan/86 vaccine were assayed for the levels of antibody against 3 subsequent, antigenically different, A/H1N1 variants. Dose-related increases in antibody responses to all 4 viruses were observed, even against a virus appearing >10 years after vaccination.

Immunogenicity, safety and consistency of new trivalent inactivated influenza vaccine.

To augment the available influenza vaccine supply, a phase III study was conducted to evaluate the immunogenicity, safety, and consistency of a new trivalent inactivated influenza vaccine manufactured by CSL Limited. Healthy adults (ages 18-64) were randomized to receive either a single dose of TIV from multi-dose vials with thimerosal, TIV from pre-filled syringes without thimerosal, or placebo. Of the TIV recipients, 97.

Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects.

To improve immune responses to influenza vaccine, a trivalent inactivated vaccine containing 60 microg of the HA of each component (A/H3N2, A/H1N1, B) was compared to a licensed vaccine containing 15 microg of the HA of each. More local and systemic reactions were reported by subjects given the high dosage but only local pain and myalgias were significantly increased. The high dosage vaccine induced a higher frequency of serum antibody increases (> or =4-fold) in both hemagglutination-inhibiting (HAI) and neutralization tests for all three vaccine viruses in the total group as well as subjects vaccinated and those not vaccinated the previous year.

A dose-response evaluation of inactivated influenza vaccine given intranasally and intramuscularly to healthy young adults.

Epidemic influenza occurs annually throughout the world and is accompanied by excess morbidity and mortality. Increasing the antigen content and topical administration of vaccine are two strategies being explored to improve the immune responses to trivalent inactivated influenza vaccine (TIV). We conducted a randomized, double-blind, placebo-controlled trial to compare the immunogenicity and reactogenicity of intramuscular (IM), intranasal (IN), or combined IM and IN administration of a contemporary US vaccine formulation at escalating dosage levels in young healthy adults.

Safety and immunogenicity of nonadjuvanted and MF59-adjuvanted influenza A/H9N2 vaccine preparations.

Background: Influenza A/H9N2 viruses can infect humans and are considered to be a pandemic threat. Effective vaccines are needed for these and other avian influenza viruses.

Methods: We performed a phase I, randomized, double-blind trial to evaluate the safety and immunogenicity of a 2-dose schedule (administered on days 0 and 28) of 4 dose levels (3.

Safety of high doses of influenza vaccine and effect on antibody responses in elderly persons.

Background: Immune responses after influenza immunization are reduced in elderly individuals, the group at greatest risk for complications and death after influenza. Improved vaccines are needed to address this problem.

Methods: Ambulatory individuals 65 years and older (N = 202) were assigned randomly to receive a single intramuscular injection of the 2001-2002 formulation of trivalent inactivated influenza vaccine containing 15, 30, or 60 microg of hemagglutinin per strain (up to 180 microg total per dose) or placebo.

Dose-related safety and immunogenicity of a trivalent baculovirus-expressed influenza-virus hemagglutinin vaccine in elderly adults.

Background: Influenza-virus hemagglutinin (HA) protein expressed in insect cells by recombinant baculovirus is a candidate influenza vaccine.

Methods: In a randomized, double-blind trial conducted in 399 adults > or = 65 years of age, the efficacy of trivalent inactivated influenza vaccine (TIV) licensed for intramuscular injection was compared with that of trivalent baculovirus-expressed HA vaccine administered at doses of 15 microg, 45 microg, or 135 microg of each HA.

Results: Compared with TIV, baculovirus-expressed HA vaccine was safe and induced better serum antibody responses to the H3 component when administered at doses of 45 microg or 135 microg of each HA.

Serum immunoglobulin G response to candidate vaccine antigens during experimental human pneumococcal colonization.

The immune response to pneumococcal surface structures during colonization was examined in a model of experimental human pneumococcal carriage. Healthy uncolonized adults were given a type 23F or 6B pneumococcus, and a portion of these subjects became colonized (6 of 14 with type 23F and 6 of 8 with type 6B). Sera from colonized and uncolonized subjects were used to determine the titer of antibody specific to pneumococcal surface components under consideration in development of noncapsular polysaccharide-based vaccines.

Chlorophyll content monitoring in sugar maple (Acer saccharum).

We conducted two experiments to determine the usefulness of a chlorophyll content meter (CCM) for the measurement of foliar chlorophyll concentration in sugar maple (Acer saccharum Marsh.) in the fall color period. In Experiment 1, four sugar maple trees were visually assigned to each of four fall foliage color categories in October 1998.

The immune response to pneumococcal proteins during experimental human carriage.

Colonization of the nasopharynx is the initial step in all infections caused by Streptococcus pneumoniae. The antibody response to carriage was examined in an experimental model of human colonization in healthy adults. Asymptomatic colonization was detected in 6/14 subjects and continued for up to 122 d.