Safety, Immunogenicity, and Surrogate Markers of Clinical Efficacy for Modified Vaccinia Ankara as a Smallpox Vaccine in HIV-Infected Subjects

Abstract

MVA is a promising candidate as a safer smallpox vaccine, even for immunocompromised individuals, a group for whom current smallpox vaccines have an unacceptable safety profile.

Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial

“…Although total antibody titers were significantly higher in healthy compared with HIV-infected vaccinia-naive subjects, PRNT GMT values were similar at the 26 week follow-up visit. This result is consistent with the results of a smaller study [16], although the trial reported here included subjects with more advanced disease (CD4 count as low as 200 cells/µL compared with >350 cells/µL). Although a suppressed immune response in HIV-infected subjects is generally expected and frequently observed with other vaccines [21], total antibody titers in HIV-infected subjects were still high and comparable to titers in healthy subjects given first- and second-generation live smallpox vaccines [14, 16], justifying the conclusion that immune responses correlating to protection had been induced in this immunocompromised population.…”

“…Modified vaccinia Ankara was also shown to induce immune responses comparable with conventional VACV-based vaccines [14, 15]. Populations at an increased risk to receive first- and second-generation smallpox vaccines (ie, subjects with HIV-infection [16], atopic dermatitis [17], or immune-suppressive therapy [18], respectively) tolerated vaccination with MVA well and had a good immune response. To further evaluate MVA as a smallpox vaccine in at-risk individuals, this Phase II trial was conducted to compare the safety and immunogenicity of MVA in HIV-infected individuals and healthy controls.…”

Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects

“…BN (primary assays) used vaccinia-Western Reserve (replicating vaccinia) [7] and BN-MVA (non-replicating vaccinia in humans) in the plaque reduction neutralizing antibody (PRNT 50 ) assay [8] and ELISA [8], respectively. Saint Louis University (SLU) (secondary assays) used ATCC MVA (VR-1508) as the assay antigens in the ELISA [30] and PRNT 60 [31] assay.…”

“…IMVAMUNE® is a modified vaccinia Ankara (MVA)-based smallpox vaccine, derived from MVA-597. IMVAMUNE ® is replicationrestricted to avian cells [4,5] and has an improved safety profile [6][7][8][9]; however, its efficacy against variola has not been tested. Both liquid and lyophilized formulations of IMVAMUNE® were tested in clinical trials.…”

Vaccinia Virus—Laboratory Tool with a Risk of Laboratory-Acquired Infection

“…Various immunization studies using highly attenuated MVA in non-human primates or in clinical trials have demonstrated promising results that MVA is safe, well tolerated, and immunogenic (Earl et al, 2004;Frey et al, 2014;Greenberg et al, 2013;Hatch et al, 2013;Walsh et al, 2013;Wilck et al, 2010). Highly attenuated vaccinia, such as MVA, was shown to minimize primary cutaneous lesions induced by a challenge with replication-competent vaccinia and to reduce viral shedding, indicating that replication-incompetent vaccinia strains could serve as a primer to modulate the immune response and allow subsequent immunization with a standard vaccinia vaccine (see the review by Walsh and Dolin [2011]).…”