a b s t r a c tIn preparation for pandemic vaccine safety monitoring, we assessed adverse events reported to the Vaccine Adverse Event Reporting System following receipt of trivalent inactivated influenza vaccines among adults from 1990 through 2005. We calculated reporting rates for nonserious, serious, and neurological adverse events. We reviewed reports of recurrent events and deaths, as well as reports identified through advanced signal detection. The most frequently reported events were local reactions and systemic symptoms. Guillain-Barré syndrome was the most frequently reported serious event (0.70 reports per million vaccinations). Adverse event reporting rates have been reasonably constant over time. No new safety concerns emerged after our review of 15 years of post-licensure surveillance data. These findings provide useful information if pandemic vaccine is rapidly distributed and pre-licensure data are limited.Published by Elsevier Ltd. BackgroundInfluenza vaccines are the primary method for the control of influenza and its complications and the most widely used type of vaccine for adults in the United States (US). The US and much of the world is preparing for the use of pandemic influenza vaccines [1]. However, even with extensive planning, limited safety data will be available for these vaccines prior to use. Safety profile highlights of the seasonal trivalent inactivated influenza vaccines (TIV) can provide a background for interpretation of adverse events that can be anticipated if pandemic influenza vaccines must be employed in the future. In addition, special importance for TIV safety monitoring stems from the 1976-1977 influenza season, when a mass vaccination effort in the US against swine influenza was halted after the vaccines appeared to be associated with an elevated risk of Guillain-Barré syndrome (GBS) [2].Placebo-controlled trials among older and healthy young adults have demonstrated that TIV administration is not associated with an increased risk of systemic symptoms (e.g., fever, malaise, myalgia); the most frequent adverse effect following vaccination is pain at the injection site [3] including anaphylaxis can occur [3], but the latter is rare [4]. A pre-licensure study of the recently licensed H5N1 vaccine identified headache, malaise, and myalgia as the most frequent systemic symptoms but also identified these at similar rates among placebo recipients [5]. Clinical trials are generally not large enough to detect rare adverse events. Post-licensure safety data provide examples of adverse event experiences among a larger and more diverse population, and reporting of adverse events following receipt of seasonal TIV to the US Vaccine Adverse Event Reporting System (VAERS) is an important source of this information. We examined 15 years of VAERS data among adults aged ≥18 years to describe patterns of adverse events after seasonal vaccines and to identify possible safety concerns that might merit intensified monitoring or evaluation. Although pandemic influenza vaccines will differ fr...

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cDNAs encoding 2 Ancylostoma-secreted proteins (ASPs), Ancylostoma ceylanicum (Ay)-ASP-1 and Ay-ASP-2, were cloned from infective third-stage larvae (L3) of the hookworm A. ceylanicum and were expressed as soluble recombinant fusion proteins secreted by the yeast Pichia pastoris. The recombinant fusion proteins were purified, adjuvant formulated, and injected intramuscularly into hamsters. Hamsters vaccinated either by oral vaccination with irradiated L3 (irL3) or by injections of the adjuvants alone served as positive and negative controls, respectively. Anti-ASP-1 and anti-ASP-2 antibody titers exceeded 1 : 100000. Each vaccinated hamster was challenged orally with 100 L3. Two groups of vaccinated hamsters (i.e., those vaccinated with either irL3 or ASP-2 formulated with Quil A) exhibited significant reductions in adult hookworm burdens, compared with control hamsters. The hookworms recovered from the hamsters vaccinated with ASP-2 plus Quil A were reduced in length. Splenomegaly, which was observed in control hamsters, was not seen in hamsters vaccinated with either irL3 or ASP-2 formulated with Quil A. These results indicate that ASP-2 is a promising molecule for the development of a hookworm vaccine.

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Laboratory dogs were vaccinated subcutaneously with 3 different recombinant fusion proteins, each precipitated with alum or calcium phosphate. The vaccinated dogs were then challenged orally with 400 third-stage infective larvae (L3) of the canine hookworm, Ancylostoma caninum. The 3 A. caninum antigens selected were Ac-TMP, an adult-specific secreted tissue inhibitor of metalloproteases; Ac-AP, an adult-specific secreted factor Xa serine protease inhibitor anticoagulant; and Ac-ARR-1, a cathepsin D-like aspartic protease. Each of the 3 groups comprised 6 male beagles (8 +/- 1 wk of age). A fourth group comprised control dogs injected with alum. All of the dogs vaccinated with Ac-TMP or Ac-APR-1 exhibited a vigorous antigen-specific antibody response, whereas only a single dog vaccinated with Ac-AP developed an antibody response. Dogs with circulating antibody responses exhibited 4.5-18% reduction in the numbers of adult hookworms recovered from the small intestines at necropsy, relative to alum-injected dogs. In contrast, there was a concomitant increase in the number of adult hookworms recovered from the colon. The increase in colonic hookworms was as high as 500%, relative to alum-injected dogs. Female adult hookworms were more likely to migrate into the colon than were males. Anti-enzyme and anti-enzyme inhibitor antibodies correlated with an alteration in adult hookworm habitat selection in the canine gastroinntestinal tract.

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Laboratory dogs were vaccinated intramuscularly with a recombinant fusion protein (expressed and isolated from Escherichia coli) formulated with the Glaxo SmithKline Adjuvant System 02 (AS02). The fusion protein encoded Ac-MTP-1, a developmentally regulated astacinlike metalloprotease secreted by host-stimulated Ancylostoma caninum third-stage larvae (L3). Control dogs were injected intramuscularly with an equivalent amount of AS02 adjuvant alone. The vaccinated and control dogs were then challenged by s.c. injection of 500 L3 of the canine hookworm A. caninum. The vaccinated dogs developed prechallenge immunoglobulin G2 (IgG2) antibody responses specific to anti-Ac-MTP-1-fusion protein with titers ranging between 1:40,000 and 1:364,000, whereas they developed antigen-specific immunoglobulin E antibody responses with titers ranging between 1:500 and 1:1,500. By immunoblotting, canine sera obtained from the vaccinated dogs recognized a protein of the estimated apparent molecular weight of Ac-MTP-1 in activated L3 secretory products. Spearman rank order correlations between the canine intestinal adult hookworm burden and quantitative egg counts at necropsy and anti-Ac-MTP-1 IgG2 antibody titers revealed a statistically significant inverse association (r = -0.89; P = 0.04), suggesting that this molecule offers promise as a recombinant vaccine.

Laboratory dogs were vaccinated subcutaneously with 3 different recombinant fusion proteins, each precipitated with alum or calcium phosphate. The vaccinated dogs were then challenged orally with 400 third-stage infective larvae (L3) of the canine hookworm, Ancylostoma caninum. The 3 A. caninum antigens selected were Ac-TMP, an adult-specific secreted tissue inhibitor of metalloproteases; Ac-AP, an adult-specific secreted factor Xa serine protease inhibitor anticoagulant; and Ac-ARR-1, a cathepsin D-like aspartic protease. Each of the 3 groups comprised 6 male beagles (8 +/- 1 wk of age). A fourth group comprised control dogs injected with alum. All of the dogs vaccinated with Ac-TMP or Ac-APR-1 exhibited a vigorous antigen-specific antibody response, whereas only a single dog vaccinated with Ac-AP developed an antibody response. Dogs with circulating antibody responses exhibited 4.5-18% reduction in the numbers of adult hookworms recovered from the small intestines at necropsy, relative to alum-injected dogs. In contrast, there was a concomitant increase in the number of adult hookworms recovered from the colon. The increase in colonic hookworms was as high as 500%, relative to alum-injected dogs. Female adult hookworms were more likely to migrate into the colon than were males. Anti-enzyme and anti-enzyme inhibitor antibodies correlated with an alteration in adult hookworm habitat selection in the canine gastroinntestinal tract.