By Heather Drost, senior editor
The Zika virus emerged on the global scene early last year and became a leading public health concern because of its ability to spread rapidly and its link to microcephaly and other severe brain defects in fetuses. One other factor that sparked international concern and jump-started a major research initiative: There is no vaccine against the Zika virus available on the market.
Zika virus cases and a brief reprieve for the US
According to the World Health Organization, 69 countries and territories have reported evidence of Zika virus transmission. In the continental United States, more than 4,600 Zika cases were associated with international travel, while another 216 cases resulted from transmission via local mosquitos in areas of Florida and Texas. Of those cases, CDC data show 1,292 occurred in pregnant women, and as of Dec. 27, 2016, 36 infants have been born with Zika-related birth defects.
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Experts expect the number of new cases in the United States to wane amidst the cooler weather this winter. Michael Kaufman, an associate professor of entomology at Michigan State University, told the Washington Times, "Mosquito season in the United States will certainly be truncated by lower temps."
U.S. territories like Puerto Rico and other Latin American countries, however, may not see a similar reprieve due to their warmer climates. In Puerto Rico, locally acquired Zika cases had reached 33,865 as of Dec. 28.
Push for a vaccine
The growing number of international cases and expected resurgence in the United States next summer is fueling the need for a Zika vaccine. The virus' rapid emergence last year sparked what a British Medical Journal editorial called a "rare" push to develop a vaccine. The editorial notes that by the time WHO held its first consultation in March, "14 active vaccine projects had already been announced." As of Jan. 5, WHO's pipeline tracker listed nearly 40 active vaccine projects launched around the world by developers in both the public and private sectors.
While most research teams are still in the non-clinical or preclinical development stages, the Inovio Pharmaceuticals and GeneOne Life Science team recently became the first to release phase I clinical trial results. The initial results, which test for safety in humans, were promising: Inovio said healthy adults who received both low doses and high doses of its GLS-5700 vaccine "demonstrated Zika antigen-specific antibody responses after one or two vaccinations" and showed no significant safety concerns. Inovio's President and CEO Joseph Kim in the release said the company plans to complete its second phase I study, which involves 160 individuals in Puerto Rico, next year and will discuss the data from both of its phase I clinical trials with regulators to determine next steps.
The National Institute of Allergy and Infectious Diseases (NIAID) also has launched phase I clinical trials for two versions of a DNA vaccine and one Zika Purified Inactivated Virus (ZPIV) vaccine being developed in collaboration with the Walter Reed Army Institute of Research, Sanofi, and the Biomedical Advanced Research and Development Authority.
NIAID Director Anthony Fauci told American Health Line that the second DNA vaccine trial was launched in December based on evidence that it would produce stronger results than the version NIAID began testing in August. Originally, NIAID planned to start a phase II clinical trial in January, but Fauci said his institute now plans to wait until mid to late February so it can compare the two phase I DNA vaccine results and move forward with one or both.
NIAID's ZPIV vaccine is being tested in multiple phase I clinical trials in different locations. But while NIAID expects the DNA vaccine to go "smoothly" from phase I to phase II when both trials are complete, Fauci said a phase II trial for ZPIV would be delayed because the institute doesn't "have enough of the product yet."
Production challenges have been cited as one of the key challenges to quick vaccine development. Stephen Thomas, an infectious diseases doctor at SUNY Upstate Medical University who previously served as the Zika program lead for the Walter Reed Army Institute of Research, noted such concerns in a New England Journal of Medicine article earlier this year. "Annual production of 100 million doses, a projected requirement, would be challenging even for the manufacturers of most licensed vaccines. Transferring technology from one organization to another, scaling up manufacturing, and securing approvals to use the vaccine could take years," Thomas wrote.
The institute also is working on three other vaccines that are all in the early testing stages:
- A chimeric Zika-Dengue vaccine, which is a live attenuated vaccine expected to begin phase I clinical trials by spring of 2017;
- An mRNA vaccine, which is in preclinical development and has yet to be tested on humans; and
- A vaccine that Fauci said "is so far [from production] and preclinical it isn't even worth mentioning."
Another team working in partnership to develop a live-attenuated vaccine is the University of Texas Medical Branch and the Brazilian Ministry of Health. UTMB researchers led by molecular biologist Pei-Yong Shi in May became the first team to replicate the Zika virus, which Shi told CNN could allow them to adapt the virus to make a safe vaccine long-term vaccine. According to WHO, the vaccine is still in the non-clinical phase.
The end game
Researchers ultimately hope to develop multiple vaccines that can be safely used for different populations and age groups, although that outcome is still years away. "You don't want one vaccine," Fauci said. However, he added, at this stage it is hard to know which vaccines stand the best chance of succeeding.
The benefit to the DNA vaccine is that is can be developed quickly because it is made with so-called platform technologies that can reduce development time. The vaccine is made by inserting a gene for Zika into a circular shape of DNA called DNA plasmids. By contrast, traditional vaccines, such as the live attenuated or ZPIV vaccines, are developed by growing batches of viruses, which can be a slow process.
Further, each type of vaccine varies in strength and durability. Fauci said, "Traditionally, the ones that give a longer lasting immunity are the ones that are either the [ZPIV] or the live attenuated," making them ideal for places where Zika become endemic and entire populations need to be vaccinated at an young ages. But, he said, "One of the problems with live attenuated [is] you can't give them to pregnant women. You have to give it to people like young children, before they grow up to reach childbearing age."
The DNA vaccine, meanwhile, can be made quickly, making it a prime candidate "to address an outbreak," Fauci said. "So there almost certainly will be more than one Zika vaccine depending on what the use of it is and what your purpose is."