DNA Flu Vaccine: Potential for Universal Protection?

US influenza activity has been rapidly increasing in the past few weeks, according torecent CDC surveillance data,and health care professionals are prepared to face a challenging flu season this year.

According to a recently-published study inPLOS One, a newly developed DNA vaccine could lead to eventual 1-dose universal protection.

According to the study, the researchers investigated the use of a universal flu DNA vaccine developed using the genetic components of the conserved areas of the influenza virus that do not change. The researchers noted that, to be successful, a universal vaccine will need antibody and T-cell responses against multiple conserved antigens, leading them to design the adjuvanted, multi-antigen DNA vaccine. The vaccine contains DNA coding for viral proteins from 4 different influenza A strains, and also includes DNA for a protein that is highly conserved.

The vaccine, developed by University of Washington researchers, is administered through the epidermis via a “gene gun” device, injecting the vaccine directly into the skin cells. The DNA vaccine is different from currently-used vaccines because it seeks out infected cells and kills them, prompting the receiver’s own skin cells to fight the infection, rather than simply repelling the virus.

To determine the vaccine’s efficacy, the researchers investigated the vaccine’s ability to induce antibody and T cell responses in 8 monkeys. The monkeys received 3 immunizations of the vaccine spaced 6 weeks apart, and the researchers examined its effects 2 weeks after each dose. After the first immunization, the researchers detected immunoglobulin G responses against each component of the vaccine. Antibody responses to the antigen were boosted after the second dose, but the titers remained unchanged following the third dose.

Overall, the vaccinated animals demonstrated significantly lower viral loads and more rapid viral clearance when compared to unvaccinated animals.

Based on the preclinical model, the researchers determined that the DNA vaccine induced very high antibody titers and robust cross-reactive T cell responses, since significant T cell responses were induced after only 1-2 doses. However, it failed to induce broadly neutralizing antibody. The researchers noted that, even in the absence of broadly neutralizing antibody, the vaccine can still provide robust protection from a highly divergent strain of influenza.

Currently licensed live-attenuated and inactivated vaccines provide significant protection against matched circulating strains, but annual reformulations are needed to keep up with antigenic drift in the viruses. Since these vaccines typically take 6-9 months to be manufactured, new vaccines cannot be produced rapidly enough to protect against the emergence of a new pandemic strain.

Focusing on the development of influenza vaccines that provide a broad spectrum of universal protection against a wider range of influenza variants, including strains with pandemic potential, can be more advantageous in the event of a pandemic threat, the researchers noted. The DNA vaccine’s 3-month production time also gives it an advantage to vaccines that take longer to develop.

Because of this, DNA vaccines are well suited for a universal influenza vaccine, they concluded.

Reference

Koday MT, Leonard JA, Munson P, et al. Multigenic DNA vaccine induces protective cross-reactive T cell responses against heterologous influenza virus in nonhuman primates.PLOS One.Published December 21, 2017.https://doi.org/10.1371/journal.pone.0189780. Accessed January 8, 2018.