Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox

Abstract

The potential use of smallpox as a biological weapon has led to the production and stockpiling of smallpox vaccine and the immunization of some healthcare workers. Another public health goal is the licensing of a safer vaccine that could benefit the millions of people advised not to take the current one because they or their contacts have increased susceptibility to severe vaccine side effects. As vaccines can no longer be tested for their ability to prevent smallpox, licensing will necessarily include comparative immunogenicity and protection studies in non-human primates. Here we compare the highly attenuated modified vaccinia virus Ankara (MVA) with the licensed Dryvax vaccine in a monkey model. After two doses of MVA or one dose of MVA followed by Dryvax, antibody binding and neutralizing titres and T-cell responses were equivalent or higher than those induced by Dryvax alone. After challenge with monkeypox virus, unimmunized animals developed more than 500 pustular skin lesions and became gravely ill or died, whereas vaccinated animals were healthy and asymptomatic, except for a small number of transient skin lesions in animals immunized only with MVA.

Clinical and immunologic responses to multiple doses of IMVAMUNE® (Modified Vaccinia Ankara) followed by Dryvax® challenge

“…The second type of analyses tested for linear trend among SC IMVAMUNE ® / IMVAMUNE ® /Dryvax ® groups receiving increasing dosages of IMVAMUNE ® (2×10 7 , 5×10 7 , and 1×10 8 TCID 50 ) in the first and the second vaccinations. In such analyses, the Cochran-Armitage trend test was used for binary outcomes at single time points.…”

“…Immunodeficient mice given a single dose of MVA survived intranasal challenge with vaccine virus strain Western Reserve (WR) [3] and animals administered intracranial injections of MVA experienced minimal encephalopathic responses [4,5]. MVA was efficacious in animal variola challenge models [6,2] and protected monkeys against a lethal monkeypox challenge [7,8].…”

Vaccination of BALB/c Mice withEscherichia coli-Expressed Vaccinia Virus Proteins A27L, B5R, and D8L Protects Mice from Lethal Vaccinia Virus Challenge

“…Although intentional release of variola virus is of great concern, other orthopoxvirus pathogens occurring in nature, such as monkeypox virus, intermittently infect human populations and pose serious health threats. Because orthopoxviruses are so highly related at the DNA level, it is predicted that any vaccine developed against one poxvirus would stimulate immunity to this entire group of viruses (9,12,13).…”

Vaccine properties of a novel marker gene-free recombinant modified vaccinia Ankara expressing immunodominant CMV antigens pp65 and IE1

“…Deletions II and III were developed and widely used for insertion of foreign genes to create recombinant MVA (rMVA) via homologous recombination [36,42]. To isolate rMVA from parental wt MVA, several screening methods were developed, including color development by metabolism of substrates by bacterial marker genes such as β-galactosidase or β-glucuronidase [43]. Selection regimes include neomycin resistance in the presence of the antibiotic G418, or E. coli guanine phosphoribosyltransferase (gpt) in the presence of mycophenolic acid [44], or host range gene selection using the properties of the K1L locus [45].…”