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In a randomized trial, the live attenuated tetravalent dengue vaccine TV003 is well-tolerated and highly immunogenic in subjects with flavivirus exposure prior to vaccination
- Source :
- PLoS Neglected Tropical Diseases, Vol 11, Iss 5, p e0005584 (2017), PLoS Neglected Tropical Diseases
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
Abstract
- Infection caused by the four serotypes of dengue virus (DENV-1-4) is a leading cause of mosquito-borne disease. Clinically-severe dengue disease is more common when secondary dengue infection occurs following prior infection with a heterologous dengue serotype. Other flaviviruses such as yellow fever virus, Japanese encephalitis virus, and Zika virus, can also elicit antibodies which are cross-reactive to DENV. As candidate dengue vaccines become available in endemic settings and for individuals who have received other flavivirus vaccines, it is important to examine vaccine safety and immunogenicity in these flavivirus-experienced populations. We performed a randomized, controlled trial of the National Institutes of Health live attenuated tetravalent dengue vaccine candidate (TV003) in fifty-eight individuals with prior exposure to flavivirus infection or vaccine. As in prior studies of this vaccine in flavivirus-naive volunteers, flavivirus-experienced subjects received two doses of vaccine six months apart and were followed closely for clinical events, laboratory changes, viremia, and neutralizing antibody titers. TV003 was well tolerated with few adverse events other than rash, which was predominately mild. Following one dose, 87% of vaccinees had an antibody response to all four serotypes (tetravalent response), suggesting a robust immune response. In addition, 76% of vaccinees were viremic; mean peak titers ranged from 0.68–1.1 log10 PFU/mL and did not differ by serotype. The second dose of TV003 was not associated with viremia, rash, or a sustained boost in antibody titers indicating that a single dose of the vaccine is likely sufficient to prevent viral replication and thus protect against disease. In comparison to the viremia and neutralizing antibody response elicited by TV003 in flavivirus-naïve subjects from prior studies, we found that subjects who were flavivirus-exposed prior to vaccination exhibited slightly higher DENV-3 viremia, higher neutralizing antibody titers to DENV-2, -3, and -4, and a higher tetravalent response frequency after TV003 administration. In summary, we demonstrate that the NIH tetravalent dengue vaccine TV003 is well-tolerated in flavivirus-experienced individuals and elicits robust post-vaccination neutralizing antibody titers. Trial registration ClinicalTrials.gov NCT01506570<br />Author summary As live-attenuated dengue vaccine candidates are developed, it is important to ascertain their safety in all populations, regardless of past exposure to dengue, closely related flaviviruses, or similar vaccines. Each of the four dengue virus (DENV) serotypes can cause clinical disease. Severe dengue disease may be life-threatening and is epidemiologically linked to secondary infection with a serotype distinct from the first infection. Candidate tetravalent dengue vaccines are designed to induce neutralizing antibody responses to all serotypes, but confirmation is needed that vaccination itself, as a secondary exposure, is not associated with the development of enhanced reactogenicity. The National Institutes of Health live attenuated tetravalent dengue vaccine candidate, TV003, has previously been shown to be safe and immunogenic in flavivirus-naïve populations. We performed a randomized, placebo-controlled clinical trial of TV003 in individuals previously exposed to flaviviruses and demonstrated tolerability and strong, broad immunogenicity across serotypes. No subjects experienced any dengue-like illness. Vaccine viremia was self-limited and occurred at acceptably low levels compared to those associated with severe dengue from natural infection. TV003 is well-tolerated in healthy adults, regardless of flavivirus exposure, and will be evaluated next in DENV-endemic settings.
- Subjects :
- Male
0301 basic medicine
Viral Diseases
Physiology
viruses
Antibody Response
Dengue virus
Antibodies, Viral
medicine.disease_cause
Biochemistry
Dengue fever
Immune Physiology
Medicine and Health Sciences
Public and Occupational Health
Neutralizing antibody
Immune Response
Vaccines
Immune System Proteins
Attenuated vaccine
lcsh:Public aspects of medicine
Viral Vaccine
virus diseases
Middle Aged
Vaccination and Immunization
Vaccination
Flavivirus
Infectious Diseases
Female
Research Article
Adult
Attenuated Vaccines
lcsh:Arctic medicine. Tropical medicine
Infectious Disease Control
Adolescent
Drug-Related Side Effects and Adverse Reactions
lcsh:RC955-962
Immunology
Dengue Vaccines
Biology
Vaccines, Attenuated
Microbiology
Antibodies
Flavivirus Infections
Young Adult
03 medical and health sciences
Double-Blind Method
Virology
medicine
Humans
Viremia
Antigens
Dengue vaccine
Public Health, Environmental and Occupational Health
Biology and Life Sciences
Proteins
Viral Vaccines
lcsh:RA1-1270
biochemical phenomena, metabolism, and nutrition
medicine.disease
biology.organism_classification
Antibodies, Neutralizing
030104 developmental biology
biology.protein
Preventive Medicine
Subjects
Details
- ISSN :
- 19352735
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- PLOS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....eb25bc6b102cf08ea949905e7b248980