As the Zika virus continues to circulate in the Americas, researchers are working to find a safe and effective vaccine to prevent infection. NIAID and its partners at the Department of Defense and the Biomedical Advanced Research and Development Authority are funding and conducting trials of several vaccine candidates. Although many of these show promise—including a DNA vaccine candidate currently in Phase 2/2b clinical trials—the search continues for a vaccine candidate that could offer immunity against the virus with a single dose. Such a vaccine would allow healthcare providers in remote, Zika-prone regions to vaccinate people faster, without the risk that their patients might miss follow-up or booster immunizations.
According to a recent study funded by NIAID, a new experimental vaccine might show promise as a single-dose candidate. The vaccine, known as ZIKV-3′UTR-LAV, uses a live but weakened version of Zika virus (called live-attenuated), and appears to induce immunity against Zika in both mice and rhesus macaques. If the vaccine ultimately proves as safe and effective in humans as it has in animals, it would be a valuable tool for healthcare providers.
In the paper, published online Sept. 22 in Nature Communications, researchers at the University of Texas Medical Branch in Galveston, the Evandro Chagas Institute in Ananindeua, Brazil, and NIAID describe experiments testing two versions of the vaccine candidate. The vaccine contained Zika virus (ZIKV) weakened through removal of key nucleotides that provide “instructions” for infecting a host. In the first version of the investigational vaccine, 10 nucleotides were deleted from the ZIKV genome, while the second version contained virus with 20 nucleotide deletions.
In the initial experiment, researchers explored the vaccine’s ability to generate an immune response in female mice, and to protect their offspring from fetal Zika infection. Because ordinary mice do not show signs of Zika disease, investigators first gave the mice an antibody to temporarily block a portion of the immune system (an interferon receptor). They gave the antibody twice: once just before administering the investigational vaccine, so that the vaccine virus could replicate and generate an immune response. The researchers then impregnated the mice and administered the antibody again, just before challenging the vaccinated pregnant mice with Zika virus infection.
While some of the pregnant mice did become infected, they had low levels of the virus in their tissues, and the majority of their placentas and fetuses showed no evidence of infection.
Zika can also cause severe damage to the testicles of male mice. In a later experiment, researchers bred male mice which lacked the gene for producing interferon, making them susceptible to ZIKV infection. Twenty-one days after being exposed to the Zika virus, the male mice that were given only a placebo injection showed an 85 to 90 percent reduction in the amount of motile sperm in their testes, and young male mice developed significantly smaller testes than their protected counterparts. However, the mice that had received either version of the vaccine showed few signs of testicular infection or damage.
The researchers also tested the candidate vaccines in a small number of rhesus macaques. Three out of four macaques given the first version of the experimental vaccine had nodetectable virus in their bodies after being challenged with ZIKV, while the fourth macaque showed low levels of the virus. However, all the vaccinated macaques did experience neutralizing antibody responses after ZIKV challenge, suggesting that they did have a low-level infection. Three additional macaques received the second version of the vaccine candidate and had no detectable virus in their bodies and no antibody response after ZIKV challenge.
Together, these results indicate that some version of the investigational ZIKV vaccine may be another good candidate for human trials, the researchers say.
C Shan et al. A Single-Dose Live-Attenuated Vaccine Prevents Zika Virus Pregnancy Transmission and Testis Damage. Nature Communications DOI: 10.1038/s41467-017-00737-8 (2017)