Differential efficacy of vaccinia virus envelope proteins administered by DNA immunisation in protection of BALB/c mice from a lethal intranasal poxvirus challenge

Abstract

DNA vaccines might offer an alternative to the live smallpox vaccine in providing protective efficacy in an orthopoxvirus (OPV) lethal respiratory challenge model. BALB/c mice were immunised with DNA vaccines coding for 10 different single vaccinia virus (VACV) membrane proteins. After an intranasal challenge with the VACV IHD strain, three gene candidates B5R, A33R and A27L produced ≥66% survival. The B5R DNA vaccine consistently produced 100% protection and exhibited greatest efficacy after three 50 g intramuscular doses in this model. Sero-conversion to these vaccines was often inconsistent, implying that antibody itself was not a correlate of protection. The B5R DNA vaccine induced a strong and consistent gamma interferon (IFN␥) response in BALB/c mice given a single DNA vaccine dose. Strong IFN␥ responses were also measured in pTB5R immunised C57BL6 mice deficient for MHC class I molecules, suggesting that the memory response was mediated by a CD4 + T cell population. Crown

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

“…Antibodies directed against A27L have potent IMV-neutralizing capacity in vitro (27). Intraperitoneal immunization of mice with Escherichia coli-expressed A27L protein or passive treatment with A27L-specific monoclonal antibodies provides full protection against lethality in a vaccinia virus challenge model (8,27,38), while a DNA vaccine encoding A27L offers partial protection (35). In addition to humoral responses, in vitro restimulation with A27L elicits cellular proliferative immune responses in splenocytes isolated from vaccinia virus-infected mice (8).…”

“…In vitro, antibodies directed against D8L have IMV-neutralizing activity, and soluble D8L protein inhibits the adsorption of wild-type vaccinia virus to cells (23). In vivo, D8L is immunogenic, and immunization of mice with a DNA vaccine encoding D8L provides partial protection from lethal vaccinia virus challenge (35). A recent study by Sakhatskyy et al has confirmed that D8L induces strong protective antibody responses in vivo and improves the efficacy of polyvalent poxvirus DNA vaccines composed of A27L and B5R or of A27L, B5R, L1R, and A33R (41).…”

“…Mice vaccinated with baculovirus-derived B5R protein are protected against lethal vaccinia virus challenge (16), and vaccination of mice with a DNA vaccine encoding B5R alone is sufficient to protect mice from lethal intranasal challenge (35). B5R also appears to stimulate cellular responses: Pulford et al have shown that a single dose of a B5R DNA vaccine induced a strong and consistent gamma interferon (IFN-␥) response in BALB/c mice (35).…”

“…The weight and ear temperature (Braun ExacTemp ear thermometer; Welch Allyn, Skaneateles Falls, NY) of each mouse were taken immediately before challenge and on alternate days starting 4 days postchallenge. Mice were also monitored daily for survival and signs of illness (disease index [DI]) and were scored as 0 (normal), 1 (slightly ruffled), 2 (clearly ruffled), 3 (hunched posture and/or conjunctivitis in addition to clear ruffling), 4 (score of 3 combined with difficulty breathing/moving/socializing), and 5 (death), as described elsewhere (35). Those with a DI of 4 and/or a Ͼ30% loss of body weight were euthanized.…”

A protein-based smallpox vaccine protects mice from vaccinia and ectromelia virus challenges when given as a prime and single boost

“…While the current licensed live vaccinia virus-based vaccine is extremely effective [3] and results in remarkably long-lived immune responses (e.g., [4]), it has an unacceptable safety profile [5,6] for wide use when considered in today's setting of global eradication of active smallpox disease. Approaches to develop safer smallpox vaccines have ranged from the study of more attenuated live vaccinia viruses (such as MVA [7][8][9] or LC16m8 [10,11]) to subunit vaccines that rely on specific viral targets delivered either as DNA plasmids [12][13][14][15] or purified proteins [16][17][18][19].…”