INO-4700 Vaccine Description
The INO-4700 MERS-CoV product is a DNA vaccine candidate, which allows for rapid design and production in response to emerging infectious diseases. Underscoring the potential for rapid deployment of DNA vaccines, INO-4700 was advanced into the clinic within nine months of preclinical vaccine candidate selection.
INO-4700 (GLS-5300) is a DNA plasmid vaccine that expresses the MERS-CoV spike (S) glycoprotein and was co-developed by GeneOne Life Science Inc. and Inovio Pharmaceuticals.
The completed Phase 1 vaccine study INO-4700 was well tolerated and induced high levels of antibody responses in 95% of subjects, while also generating broad-based T cell responses in nearly 90% of study participants. Durable antibody responses to INO-4700 used in that trial were maintained through 60 weeks following dosing.
Inovio stated expects to advance INO-4700, its candidate vaccine against MERS, into a Phase 2 field study in the Middle East and Africa where outbreaks have been observed, with full funding from CEPI.
On January 6, 2020, the company says this is the most advanced vaccine candidate for MERS.
INO-4700 Vaccine Indication
Human coronaviruses such as MERS were first identified in the mid-1960s. The best-known coronaviruses are MERS-CoV and Severe Acute Respiratory Syndrome (SARS-CoV) and the 2019 Novel Coronavirus (SARS-CoV-2).
The INO-4700 vaccine is indicated to prevent MERS, which is a deadly viral respiratory disease caused by MERS-CoV infection. To date, there is no specific treatment proven effective against this viral disease. In addition, no vaccine has been licensed to prevent MERS-CoV infection thus far.
Overall, vaccine candidates against MERS-CoV are mainly based upon the viral spike (S) protein, due to its vital role in the viral infectivity, although several studies focused on other viral proteins such as the nucleocapsid (N) protein, envelope (E) protein, and non-structural protein 16 (NSP16) have also been reported.
In general, the potential vaccine candidates can be classified into six types: viral vector-based vaccine, DNA vaccine, subunit vaccine, nanoparticle-based vaccine, inactivated-whole virus vaccine, and live-attenuated vaccines.
The majority of the identified MERS-CoV cases are nosocomially acquired via direct close contact with infected patients (Chowell et al., 2015; Cauchemez et al., 2016), whereas cases of zoonotic transmission from dromedary camels to humans were reported primarily in Saudi Arabia, where human-camel interaction is more frequent.
INO-4700 Vaccine Dosage
INOVIO's DNA medicines deliver optimized plasmids directly into cells intramuscularly or intradermally using INOVIO's proprietary hand-held smart device called CELLECTRA®.
A July 24, 2019, Phase 1 first-in-human clinical trial. Initial findings from the trial were published in The Lancet Infectious Diseases. The study, conducted at the Walter Reed Army Institute of Research (WRAIR) Clinical Trials Center, evaluated a candidate DNA vaccine INO-4700.
Overall, for those receiving 0.6 mg of INO-4700, 88% demonstrated seroconversion after a 2 dose regimen at 0 and 8 weeks, while for those receiving a 3 dose regimen given at 0, 4 and 12 weeks, 84% seroconverted after 2 doses and 100% after 3 doses, as measured by a binding antibody assay against the full-length S protein (ELISA). Additionally, 92% of the vaccine recipients in both groups displayed the ability to neutralize the virus using a neutralization assay (EMC2012-Vero neutralization).
Robust T cell responses were observed in 60% of vaccine recipients after the 2 dose regimen and 84% of those in the 3 dose group (ELISpot assay). Interestingly, a single dose of 0.6 mg of INO-4700 intradermal vaccination resulted in a 74% binding antibody response rate and a 48% neutralization antibody response rate.
INO-4700 Vaccine News
July 9, 2020 - Inovio sued by a subcontractor in the latest twist to the Covid-19 vaccine dispute.
April 28, 2020 - INOVIO and GeneOne Life Science announced interim data through week 16 from a Phase 1/2a trial of DNA vaccine INO-4700 (also called GLS-5300) for MERS-CoV. Vaccine recipients demonstrated strong antibody and T cell immune responses after 2 or 3 doses with 0.6 mg of INO-4700. The vaccination regimen was well-tolerated with no vaccine-associated severe adverse events.
July 25, 2019 - Inovio Pharmaceuticals, Inc. announced that positive results from the first-in-human trial of its vaccine against the MERS were published in The Lancet Infectious Diseases. This peer-reviewed article entitled, "Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: A phase 1, open-label, single-arm, dose-escalation trial," highlights clinical results of Inovio's collaborative vaccine study of INO-4700 (also called GLS-5300) against MERS delivered with the CELLECTRA® efficacy-enhancing device.
INO-4700 Vaccine Clinical Trials
Clinical Trial NCT04588428: Phase 2a Safety, Tolerability, and Immunogenicity of INO-4700 for MERS-CoV in 542 Healthy Volunteers - Last Update Posted on February 2, 2021
The purpose of this Phase 2a, randomized, blinded, placebo-controlled, multi-center study is to evaluate the safety, tolerability, and immunogenicity of INO-4700 administered by intradermal (ID) injection followed by electroporation (EP) using the CELLECTRA™ 2000 device in healthy adult volunteers for the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. This study is divided into 2 parts: Part 1- dose-finding stage and Part 2- dose expansion stage.
Clinical Trial NCT03721718: Evaluate the Safety, Tolerability and Immunogenicity Study of GLS-5300 in Healthy Volunteers - Last Update Posted on May 27, 2020
This Phase I/IIa study will evaluate the safety, tolerability, and immunogenicity of GLS-5300 administered intradermally (ID) followed by electroporation at 0.3 and 0.6 mg/dose assessing 2 and 3-dose regimens.
Subjects vaccinated with INO-4700 displayed robust levels of MERS antigen-specific antibody and T cell responses at week 14 (two weeks post-third dose).
These vaccine-generated immune responses to INO-4700 were durable as they were maintained through 60 weeks following dosing. Inovio's MERS DNA vaccine was well-tolerated and demonstrated overall high levels of antibody responses in 94% of subjects, while also generating broad-based T cell responses in 88% of study participants.
Furthermore, INO-4700 administration generated antibody responses with similar potency compared to those of patients who were infected with the MERS virus and subsequently recovered from the South Korea MERS outbreak.
Even more interestingly, the vaccination generated more robust T cell responses than convalescent patients, suggesting the vaccine's ability to protect from reinfection from the MERS virus.
Clinical Trial NCT02670187: Phase I, Open-Label Dose-Ranging Safety Study of GLS-5300 in 60 Healthy Volunteers - Last Update Posted on May 27, 2020
The Middle East Respiratory Syndrome Coronavirus (MERS CoV), a virus related to Severe Acute respiratory syndrome coronavirus (SARS CoV), was first recognized as a cause of severe pulmonary infection in 2012.
Infection with MERS CoV has been diagnosed in more than 1600 individuals with a mortality rate between 35% and 40%.
GLS-5300 is a DNA plasmid vaccine that expresses the MERS CoV spike (S) glycoprotein.
This study will evaluate the safety of GLS-5300 at one of three dose levels following a three-injection vaccination regimen followed by electroporation.
The study will also assess immune responses over a 1 year period with respect to the generation of antibody and cellular responses.