Inside The Dire Search for a Zika Vaccine
PRA Health Sciences
PRA Health Sciences

Absent a cure, we search for a vaccine. Edward Jenner, a country doctor living in England, performed the world’s first vaccination in 1796 for smallpox and humans have been benefiting from vaccines ever since. Today, there are more than 80 vaccines licensed for use in the US. With each new disease or outbreak there is the expected urgency to develop a vaccine, and the race is now on to find one for the Zika virus.

In most people who are infected, Zika virus produces only mild symptoms-- or no symptoms at all. Among those who have symptoms, the most common complaints are fever, rash, joint pain, and conjunctivitis (red eyes). The illness is usually mild with symptoms lasting for several days to a week after being bitten by an infected mosquito. However, Zika infection is particularly worrisome for pregnant women because it has been found to cause a severe birth defect called microcephaly. For the mothers, the diagnosis is grim. Depending on the severity of the microcephaly it can be associated with a variety of symptoms including seizures, developmental delay, intellectual disability, hearing loss and vision problems. These problems are often lifelong.

In an op-ed letter to the Washington Post, National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony Fauci, M.D. called Zika an “unprecedented threat to the people of our nation, especially pregnant women.” According to the World Health Organization, Zika is actively spreading in 70 countries and territories in the Americas, Oceania/Pacific Islands, Africa (Cape Verde), and Asia (Singapore). In the US and its territories alone the Centers for Disease Control says there have been more than 16,800 cases of Zika infection reported, with nearly 1,600 confirmed cases in pregnant women.

Several studies are underway to develop a Zika vaccine, including one that uses a similar approach to that used by another investigational vaccine developed by NIAID for West Nile virus. That shot was found to be safe and induced an immune response when tested in a preliminary trial. The potential Zika vaccine includes a small, circular piece of DNA—called a plasmid—which scientists engineered to contain genes that code for proteins of the virus. When the plasmid is injected into the arm, muscle cells read the genes and make Zika virus proteins, which self-assemble into virus-like particles. The body then develops an immune response to these particles.

The potential Zika vaccine includes a small, circular piece of DNA—called a plasmid—which scientists engineered to contain genes that code for proteins of the virus.

The testing will take place at three sites in the United States: the National Institutes of Health Clinical Center in Bethesda, Maryland; the University of Maryland's Center for Vaccine Development in Baltimore; and Emory University in Atlanta. The early-stage study will evaluate the vaccine’s safety and ability to generate an immune system response in at least 80 volunteers, ages 18 to 35. Initial results are expected by the end of 2016. If the data shows the vaccine is safe and has a favorable immune response, NIAID plans to begin testing it in Zika-endemic countries early next year.

Another vaccine, developed by Inovio Pharmaceuticals, contains a synthetic DNA fragment similar to one in the virus itself. It has been given to 160 people in Puerto Rico. Several other bio pharma companies and scientists around the world are working on a Zika vaccine, including Sanofi.

Why Zika is Stealthy and a Threat

While it’s been making headlines for the past several months, Zika isn’t new. It was first discovered in 1947 in Uganda’s Zika forest. For its first 60 years, Zika presented itself as a mild illness, but according to the WHO, the virus has changed its character and its geographic presence.

Zika virus spreads to people primarily through the bite of an infected Aedes species mosquito (Aedes aegypti and Aedes albopictus). Zika infection can also be spread by men and women to their sex partners. What makes Zika somewhat elusive is that in roughly 80% of the people it infects it rarely causes serious harm. Many people don’t even realize they’ve been infected, but the consequences for a fetus can be devastating. Zika appears to target cells that make new neurons in the brain and stops them from working properly, thereby causing the brain defects seen in some babies born with the disease. Along with microcephaly and other severe brain defects it has been linked to Guillain-Barré syndrome, an uncommon sickness of the nervous system in which a person's immune system damages nerve cells, causing muscle weakness and sometimes paralysis or death.

Most pregnant women typically worry less after their first trimester. That’s the point at which most miscarriages drop significantly and some diseases, like rubella, which can be catastrophic to fetuses in the first trimester, are less serious if a woman is infected later in pregnancy. Zika is different. A study in The Lancet finds that the virus can still cause deleterious brain defects among newborns when mothers are infected in their last trimester. A New England Journal of Medicine study also found that Zika can cause “grave outcomes” for fetuses well past the 30-week mark.

Many people don’t even realize they’ve been infected, but the consequences for a fetus can be devastating. A map of countries affected by Zika worldwide.
Zika map
Image via CDC.

History of Vaccines

Vaccines have transformed global public health. They are credited with preventing more than two million deaths each year. In the early 20th century nothing frightened parents more than polio. When a vaccine became available it was widely embraced. Today, new vaccines are not uniformly embraced. There are skeptics. Some people fear that a child’s immune system can be “overloaded” if the child receives multiple vaccines at once. Or there is the assumption that if a disease is no longer prevalent, like polio, then a vaccine is no longer necessary. In some cases, parents are fearful that vaccines cause autism. The CDC maintains there is no link between vaccines and autism.

Some researchers attribute misconceptions about vaccines to misinformation, or lack of understanding of how vaccines work. Vaccines help develop immunity by imitating an infection. This type of infection, however, does not cause illness, but it does cause the immune system to produce T-lymphocytes and antibodies. Sometimes, after getting a vaccine, as the body builds immunity, the imitation infection can cause minor symptoms, such as fever. Once the imitation infection goes away, the body is left with a supply of “memory” T-lymphocytes, as well as B-lymphocytes that help protect from infection.

Vaccines are made using different methods—some contain live viruses that have been weakened so as not to cause illness (measles, mumps, chickenpox), some are killed organisms or viruses (polio, hepatitis A, rabies), others use inactivated toxins—this is for bacterial diseases where toxins generated by the bacteria, and not the bacteria themselves, cause illness (diphtheria, tetanus), or there are subunit/conjugate vaccines which merely use segments of the pathogen (hepatitis B, influenza, pertussis).

The Economic Impact of Zika

Whatever the vaccine method used for Zika, there is no denying the sense of urgency scientists feel to develop one that will work. Children with microcephaly will require long-term specialized care. The current estimated lifetime medical cost to care for such a child is $10 million. This translates to $20 billion for every 2,000 children born with Zika virus-induced birth defects. While the physiological effects of the virus will be immense, there is also growing concern about Zika’s long-term economic impact. The World Bank estimates Zika will cost the world US$3.5 billion in 2016.

In places where the outbreak is present there is fear of a decline in tourism and foreign investment. There is ample evidence that fear is well founded. During the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak, mainland China reported a decline of US$ 2.7 billion and Hong Kong foreign direct investment inflows fell 62% in one quarter. According to the Miami Herald, six weeks after Zika officially landed in Wynwood, the virus has impacted Miami-Dade County’s economy—downtown Miami hotel bookings are down, airfare to South Florida is falling and business owners in affected areas report steep losses.

Loss of overall productivity due to Zika is another concern. Children with microcephaly may not have the ability to achieve their full cognitive potential, resulting in lower educational achievement. Zika could also result in a decrease in population growth as women of reproductive age postpone pregnancies.

In his open letter and impassioned plea for more funding to fight the Zika virus, Dr. Fauci said, “We have an obligation to meet the Zika threat and protect this country.” By extension one might argue it is imperative to protect the world from this serious health crisis.