Modified Vaccinia Ankara Virus Vaccination Provides Long-Term Protection against Nasal Rabbitpox Virus Challenge

Abstract

Modified vaccinia Ankara virus (MVA) is a smallpox vaccine candidate. This study was performed to determine if MVA vaccination provides long-term protection against rabbitpox virus (RPXV) challenge, an animal model of smallpox. Two doses of MVA provided 100% protection against a lethal intranasal RPXV challenge administered 9 months after vaccination.

FIG 1

Intramuscular immunization with MVA induces serum IgG antibodies that bind to RPXV and antibodies that neutralize RPXV. NZW rabbits (n = 4) were immunized intramuscularly with 1 × 10⁸ PFU of MVA on days 0 and 28. Naive rabbits of a similar age and housing duration were used as controls. Day 289 (prechallenge) serum for naive and MVA immunized rabbits and day 311 (postchallenge day 14) serum from MVA immunized rabbits were tested by ELISA for the presence of IgG antibodies specific for RPXV. Serum was also tested for its ability to neutralize the infectivity of RPXV. *, statistically significantly different (P < 0.05) from naive rabbits as determined by ANOVA with Tukey's multiple comparisons. No significant difference between prechallenge and postchallenge titers as determined by a paired parametric t test. MVA treated, n = 4; naïve, n = 5.

FIG 2

Intramuscular immunization with MVA provides long-term protection against RPXV. NZW rabbits (n = 4) were immunized intramuscularly with 1 × 10⁸ PFU of MVA on days 0 and 28. On day 297, rabbits were intranasally inoculated with 1 × 10⁵ PFU of rabbitpox, Utrecht strain. Rabbit body weight, temperature, and clinical signs were monitored twice each day. Rabbits reaching the humane endpoint of 5% weight loss combined with nasal or ocular discharge were euthanized. *, statistically significantly different (P < 0.05) from MVA-immunized rabbits as determined by repeated-measures 2-way ANOVA with Sidak's multiple-comparison test. Comparisons of weight and temperature were not made after day 4.5 due to <100% survival. In naive rabbits, there was a significant loss of body weight (A) and significant increase in body temperature (B) when comparing postchallenge to prechallenge absolute body weight or temperature as determined by repeated-measures one-way ANOVA (P < 0.05). Survival was statistically significantly different from that in naive rabbits, as determined by the Mantel-Cox log-rank test (P < 0.005). naïve, n = 5; MVA, n = 4 for body weight and survival, and n = 3 for temperature.