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Details about an open-label study are presented where 119 subjects were randomly assigned to receive an intradermal injection of trivalent inactivated influenza vaccine, containing 6 microgram of hemagglutinin for each antigen, and 119 to receive an intramuscular injection of the standard dose of 15 microgram of hemagglutinin for each antigen. Results of the study are presented in detail.

People who were vaccinated with smallpox in the past can still be successfully vaccinated again, according to a study of 80 people. This group was actually less likely to have a major adverse reaction to the vaccine than people who have never been vaccinated against smallpox. Even when they had a reaction, it was usually less severe.

Many people who are vaccinated with a diluted version of smallpox vaccine will not be protected against smallpox. In a study of 60 people, only 15% of those who received a 1:100 diluted vaccine produced protective antibodies against the virus, compared to 70% of those who received a 1:10 dilution and 95% of those who received the undiluted vaccine.

Smallpox vaccine diluted to a strength of 1:10 produces the same physiological response as undiluted smallpox vaccine, according to a study of 680 people. Because the supply of smallpox vaccine is limited, public health officials are considering diluting the existing vaccines so that more people can be vaccinated in the event of a bioterrorist attack.

Abstract: Currently, more than half of the world''s population has no immunity against smallpox variola major virus. This phase I double-blind, randomized trial was conducted to compare the safety and immunogenicity of two clonally derived, cell-culture manufactured vaccinia strains, ACAM1000 and ACAM2000, to the parent vaccine, Dryvax®. Thirty vaccinia-naïve subjects were enrolled into each of three groups and vaccines were administered percutaneously using a bifurcated needle at a dose of 1.0×108 PFU/mL. All subjects had a primary skin reaction indicating a successful vaccination. The adverse events, 4-fold neutralizing antibody rise and T cell immune responses were similar between the groups. [Copyright &y& Elsevier]

We developed a carboxyfluorescein succinimidyl ester (CFSE)-based flow-cytometric assay that can detect different subsets of vaccinia-specific T cells capable of both antigen-specific expansion and protective effector functions. Proliferation and effector functions were detected by CFSE dilution and intracellular staining, respectively. Absolute numbers of CD4+/CFSElo/interferon (IFN)-γ+, CD8+/CFSElo/IFN-γ+,CD8+/CFSElo/granzyme A+, and CD8+/CFSElo /CD107a+ T cells present after in vitro stimulation with live vaccinia were significantly higher in immunized individuals (P< .05). These CD4+ and CD8+ T cell increases were >2 log higher than increases detectable by standard lymphoproliferation and cytotoxicity assays. Vaccinia-specific CD8+/CFSEloIFN-γ+ and granzyme A+ T cell responses were significantly correlated with the results of standard 51Cr-release cytolytic assays (P< .05). Furthermore, vaccinia induced antigen-specific memory γδ T cells. We demonstrate that vaccinia induces robust memory effector CD4+, CD8+, and γδ T cells, all of which are relevant for protection against smallpox. CFSE-based flow-cytometric assays will be useful in evaluating cell-mediated immune responses induced by new smallpox vaccines. [ABSTRACT FROM AUTHOR]

Induction of local antibody responses to influenza A virus hemagglutinin by coadministration of two vaccines was investigated. Fifty elderly nursing home residents received inactivated trivalent influenza virus vaccine intramuscularly and simultaneously were randomized to receive either bivalent live attenuated influenza A virus vaccine or saline placebo intranasally in a blinded fashion. More significant increases in anti-H1 and -H3 IgA antibodies were detectable in nasal wash specimens of subjects who received live attenuated virus vaccine than in those who received intranasal placebo. The increased anti-hemagglutinin IgA antibody response was of longer duration in recipients of live attenuated vaccine. The change in antibody titers after vaccination was positively correlated with total blood lymphocyte counts measured before vaccination in both vaccinee groups (P < .05). There was a possible advantage of administering live attenuated with inactivated virus vaccines because of enhanced local antibody responses. [ABSTRACT FROM PUBLISHER]

Highlights: [•] Reintroduction of Variola major as an agent of bioterrorism remains a concern. [•] A compressed schedule of MVA was evaluated for use in a post event scenario. [•] MVA is well tolerated when given as two standard doses at Days 0 and 28 or 0 and 7. [•] A 2nd dose of MVA at Day 28 compared to Day 7 provided greater antibody responses. [•] INF-γ expression was greatest within 2 weeks after last vaccination. [ABSTRACT FROM AUTHOR]

Immunization with vaccinia virus elicits a protective Ab response that is almost completely CD4+ T cell dependent. A recent study in a rodent model observed a deterministic linkage between Ab and CD4+ T cell responses to particular vaccinia virus proteins suggesting that CD4+ T cell help is preferentially provided to B cells with the same protein specificity (Sette et al. 2008. Immunity 28: 847-858). However, a causal linkage between Ab and CD4+ T cell responses to vaccinia or any other large pathogen in humans has yet to be done. In this study, we measured the Ab and CD4+ T cell responses against four vaccinia viral proteins (A27L, A33R, B5R, and L1R) known to be strongly targeted by humoral and cellular responses induced by vaccinia virus vaccination in 90 recently vaccinated and 7 long-term vaccinia-immunized human donors. Our data indicate that there is no direct linkage between Ab and CD4+ T cell responses against each individual protein in both short-term and long-term immunized donors. Together with the observation that the presence of immune responses to these four proteins is linked together within donors, our data suggest that in vaccinia-immunized humans, individual viral proteins are not the primary recognition unit of CD4+ T cell help for B cells. Therefore, we have for the first time, to our knowledge, shown evidence that CD4+ T cells provide intermolecular (also known as noncognate or heterotypic) help to generate robust Ab responses against four vaccinia viral proteins in humans. [ABSTRACT FROM AUTHOR]

Modified vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus that is under consideration as an alternative to the conventional smallpox vaccine Dryvax. MVA was attenuated by extensive passage of vaccinia virus Ankara in chicken embryo fibroblasts. Several immunomodulatory genes and genes that influence host range are deleted or mutated, and replication is aborted in the late stage of infection in most nonavian cells. The effect of these mutations on immunogenicity is not well understood. Since the structural genes appear to be intact in MVA, it is hypothesized that critical targets for antibody neutralization have been retained. To test this, we probed microarrays of the Western Reserve (WR) proteome with sera from humans and macaques after MVA and Dryvax vaccination. As most protein sequences of MVA are 97 to 99% identical to those of other vaccinia virus strains, extensive binding cross-reactivity is expected, except for those deleted or truncated. Despite different hosts and immunization regimens, the MVA and Dryvax antibody profiles were broadly similar, with antibodies against membrane and core proteins being the best conserved. The responses to nonstructural proteins were less well conserved, although these are not expected to influence virus neutralization. The broadest antibody response was obtained for hyperimmune rabbits with WR, which is pathogenic in rabbits. These data indicate that, despite the mutations and deletions in MVA, its overall immunogenicity is broadly comparable to that of Dryvax, particularly at the level of antibodies to membrane proteins. The work supports other information suggesting that MVA may be a useful alternative to Dryvax. [ABSTRACT FROM AUTHOR]