Rapid and Long-Term Immunity Elicited by DNA-Encoded Antibody Prophylaxis and DNA Vaccination Against Chikungunya Virus

Abstract

A DNA-based dMAb strategy induced rapid protection against an emerging viral infection. This method can be combined with DNA vaccination as a novel strategy to provide both short- and long-term protection against this emerging infectious disease. These studies have implications for pathogen treatment and control strategies.

In Vivo Production of Monoclonal Antibodies by Gene Transfer via Electroporation Protects against Lethal Influenza and Ebola Infections

“…Despite lower inoculum of pDNA, we observed higher mAb expression with mean peak serum concentrations (3–5 μg/mL) (Figure 2) that are 3- to 10-fold higher than previous findings 13, 14, 15, 16, 17. Furthermore, mAb concentrations remained ∼1 μg/mL for up to 32 weeks (Figure 2), which is more persistent that previously described,14, 16, 17 therefore potentially extending the therapeutic window for treatment and prevention. The observed serum antibody concentrations fall well within the therapeutic range for many mAbs in clinical use today,1, 36 and the duration of antibody expression bodes well for infrequent administration of pDNA/EP.…”

“…We believe our in-depth studies have moved pDNA/EP beyond preliminary reports, placing this platform technology on a solid foundation for clinical development. For our efficacy experiments in mice, we used doses of pDNA (5–10 μg) that are scalable for humans, in contrast to previous studies (25–300 μg) 11, 12, 13, 14, 15, 16, 17. Despite lower inoculum of pDNA, we observed higher mAb expression with mean peak serum concentrations (3–5 μg/mL) (Figure 2) that are 3- to 10-fold higher than previous findings 13, 14, 15, 16, 17.…”

“…For our efficacy experiments in mice, we used doses of pDNA (5–10 μg) that are scalable for humans, in contrast to previous studies (25–300 μg) 11, 12, 13, 14, 15, 16, 17. Despite lower inoculum of pDNA, we observed higher mAb expression with mean peak serum concentrations (3–5 μg/mL) (Figure 2) that are 3- to 10-fold higher than previous findings 13, 14, 15, 16, 17. Furthermore, mAb concentrations remained ∼1 μg/mL for up to 32 weeks (Figure 2), which is more persistent that previously described,14, 16, 17 therefore potentially extending the therapeutic window for treatment and prevention.…”

“…Presumably, mAbs are expressed endogenously by transduced muscle cells and released into the circulation. Previous studies on pDNA/EP for antibody gene transfer have shown that mAbs produced in vivo are functionally intact and can protect mice from influenza,11, 12 Dengue, 13 or Chikungunya virus challenge 14 . Although some of these studies demonstrated persistence of appreciable in vivo antibody productions for weeks to months,11, 12, 13, 14 others did not 15, 16, 17.…”

Vaccines for epidemic infections and the role of CEPI

“…39,40 Among the factors that make vaccine development relatively easy is the fact that Chikungunya is an avirus with a genome that synthesizes envelope proteins against which antibodies are typically effective. 41 Although there are multiple lineages of the virus, depending on geography, there is only one serotype. Moreover, years ago formalin-inactivated and attenuated Chikungunya vaccines were developed and shown to induce neutralizing antibodies in humans.…”