The results of phase 1 trials of two different types of Zika vaccines, one of them an inactivated vaccine recently filed by Sanofi on unstable research support and other challenges, were found to be safe and immunogenic.
One of the studies focused on two different versions of a DNA-based vaccine, while the other details the findings of the inactivated vaccine. Work on both vaccines was carried out with the support of the National Institute of Allergy and Infectious Diseases (NIAID), and both studies were published yesterday in The Lancet .
A dramatic fall in Zika cases prompted the US government. to reorganize their research priorities related to Zika. About 2 months ago, Sanofi announced that it was halting work on its inactive candidate for the Zika vaccine in the face of funding cuts by the Advanced Biomedical Research and Development Authority (BARDA). In addition, a license agreement from the US Army. UU With Sanofi he encountered harsh political obstacles, and some politicians urged the government to guarantee an agreement to limit the price of the resulting vaccine.
About 20 vaccines against Zika are in various stages of development.
Inactivated vaccine Results
The inactivated vaccine test (ZPIV), developed by scientists from the Walter Reed Army Research Institute (WRAIR), took place at three sites in the USA. UU and involved 67 adults, including 55 who received the vaccine with adjuvant with aluminum salt. and 12 who received placebo. Participants received two intramuscular injections of the same dose 4 weeks apart.
More than 90% of those who received the inactivated vaccine had detectable antibodies against Zika virus within 4 weeks after the last dose.
Although the antibody concentration needed to protect infants from congenital Zika infection has not been determined, the researchers demonstrated that antibodies in the blood of participants who received the vaccine provided solid protection to the mice that were infected experimentally with the Zika virus.
Anthony Fauci, MD, NIAID director, said in a press release that a vaccine against Zika is urgently needed to protect babies from related birth defects and adults and children from other health problems related to the virus. "We are encouraged by the results of initial clinical trials that indicate that the ZPIV vaccine is safe and immunogenic, data that support additional clinical trials of the vaccine to determine its ability to prevent Zika virus infection," he said.
Col Nelson Michael, MD PhD, who directs the Zika program at WRAIR, said in the NIAID statement: "Zika continues to be a threat to US military personnel and the families of service members. Our goal is to develop a vaccine to protect the army and the global community. "
The next research steps for the WRAIR vaccine are to evaluate dosing, scheduling and prior immunity. To examine how pre-existing immunity could affect the vaccine response, WRAIR is vaccinating participants with yellow fever or Japanese encephalitis vaccine before testing the ZPIV regimen. The three viruses are members of the flavivirus family.
In addition, a study will be conducted in Puerto Rico on people who have been exposed to the flavivirus naturally, such as through a previous dengue infection. Meanwhile, other US studies UU They will assign participants a high, moderate or low dose to measure the optimal dosage and another will evaluate several dosage programs.
Nelson told Reuters that the Army was exploring authorization of the ZPIV vaccine to other companies.
One DNA vaccine outperformed another
The second study tested two forms of a DNA-based vaccine created by NIAID scientists shortly after reports surfacing that linked Zika infection during pregnancy with birth defects . The vaccines contain a small circular piece of DNA called a plasmid, in which the researchers inserted genes that encode two surface proteins of the Zika virus.
The team tested two different plasmids: VRC5288 and VRC5283. The trial version of VRC5288 was launched in August 2016 and involved 80 healthy volunteers between 18 and 35 years of age in three US sites. UU They received two or three doses at different time intervals of 4 milligrams (mg) per needle and syringe in the arm muscle, at least 4 weeks apart.
Meanwhile, the VRC5283 vaccine trial began in December 2016 at the National Center for Clinical Health Institutes and involved 45 healthy volunteers between 18 and 50 years of age. Each received two or three doses of 4 mg at various time intervals. The researchers also compared two methods of administering the vaccine: needle plus syringe or needleless injector, to see which was the most immunogenic. In addition, some participants received the dose of a complete vaccine divided with an injection administered to each arm.
In addition to mild to moderate reactions such as sensitivity or redness at the site of injection, the vaccine was safe and well tolerated by people in both trials.
The analysis of blood samples obtained 4 weeks after the final vaccination found that 60% to 89% of those who received the VRC5288 version had a neutralizing antibody response, which was lower than 77% to 100% of the participants who got that answer after receiving the VRC5283 vaccine.
In the vaccine trial containing the plasmid VRC5283, participants who were immunized with the needleless injector had the highest neutralizing antibody response levels, and those who received a divided dose administered to both arms had a response more robust than those who received the full dose in one arm.
Researchers determined that the VRC5283 vaccine was the most promising and carried it forward to an international efficacy trial in March 2017, with the goal of enrolling at least 2,490 healthy volunteers in areas with confirmed or potentially active Zika transmission. US states UU., Puerto Rico, Central America and South America.
In an independent press release from NIAID, Fauci said the promising results from phase 1 support the phase 2 trial. According to NIAID, the objectives of the study are also to further assess its safety and immunogenicity and determine if you can prevent Zika infection.
Key Questions Unanswered
In a commentary The Lancet in both studies, two experts from the Center for Vaccine Research at the University of Pittsburgh, one of whom also works at the Fiocruz Institute of Brazil, wrote that having multiple promising candidates for vaccines within two years of identifying the link between Zika and microcephaly is impressive.
wrote that the results of both trials are promising, but more research is needed to address the key questions. One is whether the viral antigens in the vaccine could cross-react with the host molecules. "A complete understanding of the mechanism of Guillain-Barre syndrome associated with the Zika virus could be crucial to ensure the safety of the vaccine," they added.
In addition, they raised concerns about the possibility of whether Zika immunity from vaccination can alter the behavior of other flaviviruses, such as dengue virus or dengue vaccination, which could have a clinical impact.
Other challenges are field efficacy tests, given the Zika pattern of rapidly emerging bursts followed by a rapid decline and the difficulty of performing trials on non-pregnant participants with a disease that has mild symptoms.
"A rapid and accurate assessment of the effectiveness of the Zika vaccine probably requires an understanding of the general correlates of protection and the mechanisms involved in fetal infection," the authors wrote. They noted that almost 30 years have passed before the rubella vaccine becomes available, and although the incidence of Zika has decreased in most countries, its spread has been widespread and unpredictable.
"A vaccine is still urgently needed to protect against congenital Zika syndrome," they conclude.
December 4 Lancet inactivates the study of the Zika vaccine
December 4 NIAID press release on the trial of the inactivated Zika vaccine
Dec 4 Reuters story
December 4 Lancet Zika DNA vaccine study
Dec 4 NIAID press release on DNA vaccine assays
] December 4 Comment by Lancet