We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.

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. Susceptibility to carriage did not correlate with total serum immunoglobulin (Ig)G to the homotypic capsular polysaccharide. All of the colonized subjects, in contrast, developed a serum IgG and secretory IgA response to a 22 kD protein, whereas 7 of 8 subjects who did not become colonized had preexisting antibody to this protein. Analysis of the 22 kD protein identified it as the NH2-terminal region of pneumococcal surface protein A (PspA). Our findings provide evidence for the role of antibody to this protein fragment in preventing pneumococcal carriage by humans.

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The improved immunogenicity of high-dose influenza vaccine among elderly persons should lead to enhanced protection against naturally occurring influenza.

To improve immune responses to influenza vaccine, a trivalent inactivated vaccine containing 60 µg of the HA of each component (A/H3N2, A/H1N1, B) was compared to a licensed vaccine containing 15 µg 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 (≥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. Mean titers of antibody attained, the magnitude of antibody increases and the frequencies of persons with final HAI antibody titers ≥1:32, ≥1:64, and ≥1:128 were all greater for the high dosage group in both serologic tests, for all groups, and for all vaccine viruses. These increased immune responses should provide increased protection against influenza in the elderly. KeywordsInfluenza; vaccines; elderly IntroductionTrivalent inactivated influenza vaccines (TIV) are effective for prevention of influenza and its complications among the elderly. However, there is a need to improve these vaccines because the degree of protection is variable and sometimes low [1,2]. One option for improving TIV is to increase vaccine dosage so as to increase serum antibody responses to the hemagglutinin (HA) as measured in hemagglutination-inhibiting (HAI) and neutralization (neut) tests. Increasing antibody to the HA in serum correlates with increasing protection against infection and illness after exposure to influenza and available information indicates that this antibody is the primary mediator of immunity to infection [3,5].A number of studies have shown that increasing the dosage of TIV will induce an increase in the serum antibody response [6][7][8][9][10][11][12][13][14][15][16][17][18]. Dosages as high as 135 µg of each HA in TIV (containing an A/H3N2, A/H1N1 and B virus strain) have been shown to be safe in elderly subjects and to induce significantly greater serum antibody responses as dosage was increased [15,17]. In a recent study, we tested the 2000-2001 formulation of licensed trivalent vaccine containing the standard 15 µg of the HA of each component as well as unlicensed concentrations of the same vaccine containing 30 ug and 60 ug of each HA; the increased dosage was well tolerated and induced an increased antibody response [16]. To confirm this finding and to evaluate a high dosage vaccine designed for clinical development, a larger number of elderly subjects were given a new 60 µg per HA TIV. The gelatin and thimerosal components in licensed vaccine were removed and only the three viral components used in [2004][2005] Materials and Methods Study DesignThis was a multi-site, phase II, randomized, double-blind, stratified study. The primary hypothesis was that the new TIV containing 60 µg of each antigen would be well tolerated and induce a significantly greater serum HAI ...

The combination of MF59 adjuvant with a subunit vaccine was associated with improved immune responses to an influenza A/H9N2 virus. The adjuvanted vaccine was immunogenic even after a single dose, raising the possibility that a 1-dose vaccination strategy may be attainable with the use of adjuvanted vaccine.

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 60 μg of the hemagglutinin of each strain induced significantly more serum anti-HA antibody among elderly persons than did the standard vaccine containing 15 ug 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 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptVaccine. Author manuscript; available in PMC 2011 February 25. in that study. The high dosage vaccine contained eight times as much NA activity as the standard vaccine and induced a significantly higher frequency of antibody responses and higher mean postvaccination anti-NA titers to the N1 and N2 of the A/H1N1 and A/H3N2 viruses in the vaccines than did the standard vaccine. Ensuring an increased antibody response to the NA antigen in inactivated influenza virus vaccines should increase the protection against influenza. An increased quantity of the NA antigen in the vaccine will ensure an increased response.

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