The combined effort of researchers at NanoBio and the Michigan Nanotechnology Institute for Medicine and Biological Sciences at the University of Michigan led to the very significant discovery of a new NE adjuvant formulation (NE02) that is optimal for intramuscular administration. Given most vaccines today are injected, this NE formulation has the potential to enhance the effectiveness of many intramuscular vaccines currently available as well as those in development.
As reflected in the chart below, NE02 formulations demonstrate high antigen uptake in vitro along with low cell cytotoxicity, enabling the use of a broad range of concentrations with intramuscular administration. Formulations of up to 40% NE02 have been shown to be well tolerated in mice, with reactogenicity scores similar to IM Alum.
Initial IM NE02 Vaccine Studies in Mice
Numerous studies in mice have demonstrated that intramuscular NE02 vaccination elicits robust antibody responses as well as balanced cellular immunity. In the mouse study represented by the chart below, three IM administrations of a 5% NE02-rH5 (plant-based) vaccine elicited protective HAI titers in 88% of animals, compared to 0% in the control arms:
In addition, the NE02 vaccine elicited a robust and balanced Th1/Th2 response, as measured by INFʏ and IL-5 in the two charts below:
A second study combining IM NE02 and RSV F Protein from Sino Biological, Inc. showed a similar robust antibody and cell-mediated immune response. The charts below reflect the serum IgG response following one or two vaccinations:
The serum neutralization activity after two vaccinations is reflected in the following chart:
In terms of cellular immunity, the NE02 arms again elicited a robust and balanced Th1/Th2 response, as measured by INFʏ and IL-5:
Combining NE02 With Other IM Adjuvants
Further mouse experiments have explored whether NE02 is compatible with other intramuscular vaccine adjuvants. In studies testing such combination-adjuvant vaccines, we observe significant synergy particularly with respect to cell-mediated immunity.
Below we show serum IgG antibody responses in mice following two IM vaccinations of rH5 antigen mixed with (i) 5% NE02, (ii) CpG, and (iii) both adjuvants combined.
We note a one log increase in serum antibodies from the combination adjuvant vaccine, as compared to the vaccine with either adjuvant alone. Even more striking is the synergistic effect observed on the cellular response shown below. In the following chart, we show a marked increase in the Th1 response from the combination adjuvant vaccine as measured by INFʏ. In parallel the Th2 (IL-5) response is completely quenched when the two adjuvants are used together.
The above data demonstrate that the compatibility of NE02 with other IM adjuvants may play an important role in the development of intramuscular vaccines that elicit the desired immune response required for durable efficacy against selected infectious diseases, cancers and allergies.
NanoBio is currently collaborating with several partners testing IM NE02 vaccine candidates for selected diseases of interest.