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

Questions regarding the safety and duration of immunity following live yellow fever vaccination

“…In contrast, MVA is a further-attenuated, replication-deficient strain of vaccinia that is unable to establish an acute infection in humans and is therefore rapidly cleared. Antiviral immune responses to this over-attenuated strain of vaccinia are lower than that achieved with wild-type vaccine strains of replication-competent vaccinia (Figure 3A) and antiviral immunity declines sharply even after 2 or 3 doses of vaccine have been administered [52,53]. For example, within 6 months after a second vaccination as few as 35–54% of subjects maintain a measurable neutralizing antibody titer of PRNT 50 ≥10 [52].…”

“…Antiviral immune responses to this over-attenuated strain of vaccinia are lower than that achieved with wild-type vaccine strains of replication-competent vaccinia (Figure 3A) and antiviral immunity declines sharply even after 2 or 3 doses of vaccine have been administered [52,53]. For example, within 6 months after a second vaccination as few as 35–54% of subjects maintain a measurable neutralizing antibody titer of PRNT 50 ≥10 [52]. Despite reaching peak geometric mean neutralization titers of up to 77.6 shortly after booster vaccination, by the 6 month time point the antiviral antibody titers of the remaining seropositive subjects ranged from 11.7 to 10.2 which is near the limit of detection (PRNT 50 = 10).…”

“…Dryvax is able to replicate locally in the skin for several days or weeks after inoculation and this induces a long-lived immune response in the majority of vaccine recipients [49,50]. MVA is replication-deficient and the virus is rapidly cleared, resulting in lower antibody responses that decay more rapidly than that observed with Dryvax [52,53]. (B) YFV-17D vaccine strains of virus elicit a viremic infection of variable magnitude and duration [56].…”

Defending against smallpox: a focus on vaccines

“…Similarly, the vaccine was tested in HIV-infected patients and was demonstrated to be safe, immunogenic, and well tolerated, without cardiac complications [118]. Lyophilization of MVA-based vaccines for long-term stable storage has been shown not to affect immunogenicity, and intradermal injection of low doses has been demonstrated to have similar immunogenicity to the standard subcutaneous injection route typically used in smallpox vaccination [119]. As a result of such studies, IMVAMUNE was added to the U.S. National Strategic Stockpile in 2010 for individuals with HIV and atopic dermatitis, and since has been approved for the entire adult population in Europe and in Canada for adults with immune deficiencies or skin disorders.…”

Vaccinating against monkeypox in the Democratic Republic of the Congo

“…These were overcome by the use of solar-powered refrigerators in conjunction with cold boxes such as the Credo cube for vaccine transport. The transition of IMVAMUNE from a liquid frozen to a lyophilized formulation has the potential to improve the cold chain parameters and simplify usage in the field (Frey et al, 2015). Other challenges included those that were foreseen, such as how to avoid of exhaustion of supply inventories, and others we did not anticipate, such as staff fatigue which mounted over the 16 weeks required for initial enrollment of participants.…”