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Abstract: Smallpox vaccination with replication deficient vaccinia strains such as Modified Vaccinia Ankara (MVA) may induce protective immunity with improved safety and tolerability profiles compared with currently available smallpox vaccines. Ninety subjects were randomized equally to six groups in a partially blinded, randomized, controlled clinical trial. IMVAMUNE® (MVA-BN®, Bavarian Nordic A/S, Kvistgård, Denmark) vaccine or placebo was administered at Study Days 0 and 28 by subcutaneous or intramuscular injection and five groups were challenged with Dryvax® at study Day 112. Vaccination with two doses of IMVAMUNE® was safe and well tolerated compared to Dryvax®. IMVAMUNE® produced comparable cellular and humoral immune responses to one dose of Dryvax® and the immunity induced appears robust 90 days post-vaccination by evidence of attenuated primary cutaneous reaction responses following Dryvax®. IMVAMUNE® vaccination prior to Dryvax® reduced virus replication at the Dryvax® site, decreased the size of the primary cutaneous lesion, and decreased the time to healing but did not completely ameliorate the immune response. [Copyright &y& Elsevier]

Background. Innate immunity, including Toll-like receptor (TLR)-mediated expression of the B7 costimulatory molecules CD80 and CD86, is critical for vaccine immunity. We examined whether CD80 and CD86 expression vary with aging and predict response to the trivalent inactivated influenza vaccine. Methods. One hundred sixty-two subjects between 21 and 30 years of age (the young group) or ⩾65 years of age (the older group) enrolled before vaccination. We determined TLR-induced monocyte CD80/CD86 expression by flow cytometry and vaccine antibody responses by hemagglutination inhibition. Results. The mean increase in TLR-induced CD80+ monocytes was reduced in older, compared with young, adults by 68% (P = .0002), and each decile increase of CD80+ cells was associated with an 8.5% increase in mean number of vaccine strains with a ⩾4-fold titer increase (P = .01) and a 3.8% increase in mean number of strains with a postvaccine titer ⩾1:64 (P = .037). Each decile decrease of CD86+ cells was associated with an 11% increase in the mean number of strains with a 4-fold increase (P = .002) and a 3.9% increase in the mean number of strains with a postvaccine titer ⩾1:64 (P = .07). Conclusions. CD80 and CD86 expression on activated monocytes is highly associated with influenza vaccine response. This approach prospectively identifies adults unlikely to respond to immunization who may benefit from alternative vaccines or antiviral prophylaxis during influenza outbreaks. [ABSTRACT FROM AUTHOR]

Background. Chronically ill older adults constitute a population vulnerable for complications associated with influenza. Study of their immunity to influenza virus may help design better strategies to stimulate protective immune responses. Methods. Immunogenicity of influenza vaccines and immune protection from natural influenza were assessed in older adults with chronic obstructive pulmonary disease as part of a vaccine efficacy trial. Subjects received either trivalent inactivated influenza virus vaccine (TVV) intramuscularly and trivalent live cold-adapted influenza virus vaccine (CAIV-T; n = 1107) intranasally (inl) or TVV and placebo inl (P; n = 1108). Results. In the subsets of study subjects assessed, serum hemagglutination inhibition (HAI) and nasal-wash antihemagglutinin (HA) immunoglobulin (Ig) A and IgG antibody levels and anti-influenza virus CD8+ cytotoxic T lymphocyte activity increased after immunization. Mean postimmunization nasal-wash IgA antibody levels to influenza A H3/HA and B HA were statistically higher in the group (n = 957 ) than in the TVV+CAIV-T group ( n = 951). Postimmunization serum HAI and nasal-wash IgA antibodies to influenza A/H3N2 TVV+P and B viruses were associated with a reduced relative risk for natural influenza infection. Conclusions. appeared more immunogenic than , but the observed difference may TVV+CAIV-T TVV+P be clinically unimportant. Anti-influenza serum and nasal-wash antibodies were associated with immuneprotection. [ABSTRACT FROM AUTHOR]