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Biosecurity Briefing
Study Shows New Adjuvant, Nasal Spray Vaccine May Offer Protection against Anthrax By Shana R. Deitch and Jennifer Nuzzo, August 24, 2007 According to a study published in the August 2007 issue of the journal Infection and Immunity, anthrax vaccine with a new adjuvant administered nasally provided guinea pigs greater protection against lethal doses of anthrax than the standard vaccine administered by injection.1 According to the study, currently licensed anthrax vaccines, which were developed more than 30 years ago, are not ideal because they are “associated with local side effects” from their alum adjuvants and because they require yearly booster injections. In the pursuit of a safer, more effective vaccine candidate, the study researchers tested the efficacy and safety of an anthrax vaccine containing a new adjuvant—a soybean oil nanoemulsion mucosal adjuvant—in mice and guinea pigs. The study notes that although other mucosal adjuvants used for vaccine development have caused safety concerns, nanoemulsion adjuvant used in previous experiments has resulted in safe and effective “broad antimicrobial activity.”1 Mice used in this study were not exposed to anthrax. Instead, mice were used to examine the effectiveness (as measured by the production of antibodies) of the nanoemulsion adjuvant in comparison to other adjuvants. To that end, mice were vaccinated (administered nasally) at day zero and again at three weeks. Mice were assigned to groups that received one of the following vaccines (n=5 mice assigned to each vaccine group):
In the mouse study, the researchers noted that intranasal vaccination with rPA plus nanoemulsion solution resulted in statistically significant higher titers of protective antibodies than in animals who received vaccines containing rPA alone, rPA plus alum, and rPA plus the two other adjuvants. Among the mice immunized with the four varying concentrations of nanoemulsion solution, lower antibody levels were observed in the groups of mice that received both the 0.1% and 0.5% concentrations.1 However, no significant difference in immune response was seen in mice receiving either the 1% or 2% concentrations. Consequently, the researchers used the 1% nanoemulsion solution to compare the efficacy of the nanoemulsion vaccine to the efficacy of the vaccines containing rPA plus saline or the other adjuvants (alum, MPL-A, CpG). Guinea pigs, which are considered to be the “primary model” for anthrax vaccine efficacy testing, were vaccinated at day one and again at four weeks. Guinea pigs were assigned to either receive 10, 50, or 100 micrograms of rPA plus 1% nanoemulsion solution (n=10 guinea pigs per experimental group). The control groups received the same concentration of rPA mixed with saline instead of the nanoemulsion solution (n=10 per group). Guinea pigs were exposed to anthrax spores either via intradermal injection at 1000 times the dose required to be lethal to 50% of the population (LD50), or inhalational application at either 10 or 100 times the LD50, 5 months after the final vaccination. The nanoemulsion vaccine produced 100% protection in the intradermal anthrax challenge, while none of the control guinea pigs survived. Similarly, none of the control animals survived the inhalational challenge. Among those that received the nanoemulsion vaccine in the inhalational challenge, survival rates were as follows: 70% for those guinea pigs that received 10 times the lethal dose and 40% for those that received 100 times the lethal dose. According to the authors, the lower survival rates observed in the inhalational challenge are consistent with the effectiveness of other vaccines’ survival rates for inhalational anthrax.1 However, the authors point out that intranasal vaccination with the nanoemulsion solution did delay the guinea pigs’ time to death by three to five days, which could provide a “potential therapeutic advantage” if rPA/nanoemulsion vaccination were used post-exposure in combination with antibiotics or monoclonal antibodies.1 Based on these results, the authors conclude that the nanoemulsion adjuvant can safely increase the efficacy of rPA for intranasal vaccination, which “potentially could lead to a needle-free anthrax vaccine requiring fewer doses and having fewer side effects than the currently available human vaccine.”1 References
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