Get the content you want anytime you want.
REGISTER NOW | SIGN IN
ARTICLE

Intradermal Ebola Vaccine Candidate Shows 100% Seroreactivity After 2 Doses

APR 04, 2019 | JONNA LORENZ
Intradermal administration of a DNA Ebola vaccine candidate using electroporation showed improvements over intramuscular administration in a recent study that found the new approach to Ebola prevention to be well-tolerated and effective.

In the investigation, published in The Journal of Infectious Diseases, investigators at the University of Pennsylvania and Inovio Pharmaceuticals aimed to study a safe and temperature-stable immunogenic vaccine to prevent Ebola outbreaks. They found favorable results for intradermal administration of the vaccine candidate INO-4201.

"A 2-dose immunization schedule could be used as pre-exposure prophylaxis to first responders, military personnel, those living in at-risk regions, and travelers," investigators wrote, adding that intradermal delivery of INO-4201 "addresses or surpasses the critical characteristics for reactive use that can be assessed at this stage of development."

The study also noted that the electroporation is less burdensome than cold-chain maintenance and is portable and easy to charge.

Delivery via SynCon synthetic DNA vaccines by CELLECTRA electroporation devices allows the vaccine to be rapidly deployed, according to the study, which was the first direct clinical comparison of intramuscular and intradermal delivery using electroporation.

The phase 1 clinical trial examined vaccine candidates INO-4201, designed with 14 Ebolavirus GP sequences from outbreaks in Zaire; INO-4202, which matches Zaire Makona Ebolavirus with clinical isolates from the 2014 West African outbreak; INO-4212, which is a combination of the 2; and INO-9012, which encodes human interleukin-12.

The trial involved 5 cohorts of 15 participants each, with vaccines administered at 0, 4, and 12 weeks followed by CELLECTRA controlled electrical impulses. Cohort 1 received INO-4201 intramuscularly. Cohort 2 received INO-4202 intramuscularly. Cohort 3 received INO-4201 intradermally. Cohort 4 received INO-4212 intramuscularly. Cohort 5 received INO-4212 plus INO-9012 intramuscularly.

Antibodies to the Ebola virus glycoprotein were generated in all 5 cohorts, most rapidly in the intradermal cohort, which saw higher geometric mean titers of GP-specific antibodies (15 after 1 dose, 3722 after 2 and 5219 after 3) than the intramuscular group (1, 78, 998) and T-cell responses in more than 70% of participants.

Participants who received the vaccine intramuscularly reported pain more often than those who received intradermal administration (73% compared with 40%). Visual analog scale scores (assessing pain) were also lower in the intradermal group. Adverse events including myalgia, fatigue, headache, and malaise were more common in the groups that received intramuscular administration.

Only the intradermal cohort 3 saw 100% seroreactivity after 2 immunizations. Although no seroreactivity was observed following a single intramuscular immunization of INO-4201, 38% of participants in the intradermal group displayed seroreactivity after a single immunization. In the intramuscular group, seroreactivity jumped to 53% after 2 doses and 87% after 3 compared with 100% after just 2 doses in the intradermal group.

The study noted that responses after 2 doses in the intradermal electroporation cohort were similar to rVSV-ZEBOV, which is the most extensively evaluated vaccine candidate, and persisted for more than a year in most subjects. The rVSV-ZEBOV is the only vaccine being deployed in the current Ebola outbreak in the Democratic Republic of the Congo.

"In this clinical study, vaccines were administered 3 times with no negative impact on immongenicity and continued immune boosting," the study concluded. "This supports the potential to retain long-term immunity as well as reuse of DNA as a 'vector' for additional vaccine candidates targeting other infectious disease pathogens in the same individuals."

Efforts to vaccinate have been crucial to limiting the spread of the Ebola virus in the Democratic Republic of the Congo, where ongoing violence has complicated response efforts.

For the most recent case counts in the Ebola outbreak in the Democratic Republic of the Congo, visit the Contagion® Outbreak Monitor.
To stay informed on the latest in infectious disease news and developments, please sign up for our weekly newsletter.


FEATURED
Big advances in treatment can't make up for an inability to stop new infections, which number 5,000 per day worldwide.