Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults

Kirkpatrick, Beth D.; Durbin, Anna P.; Pierce, Kristen K.; Carmolli, Marya P.; Tibery, Cecilia M.; Grier, Palmtama L.; Hynes, Noreen A.; Diehl, Sean A.; Elwood, Dan; Jarvis, Adrienne P.; Sabundayo, Beulah P.; Lyon, Caroline E.; Larsson, Catherine J.; Jo, Matthew; Lovchik, Janece M.; Luke, Catherine J.; Walsh, Mary Claire; Fraser, Ellen A.; Subbarao, Kanta; Whitehead, Steven S.

doi:10.1093/infdis/jiv082

Cited by 165 publications

(192 citation statements)

References 24 publications

Supporting

Mentioning

184

Contrasting

Order By: Relevance

“…Healthy donors were enrolled and vaccinated with TV005, a tetravalent DENV vaccine formulation. Blood samples were collected as a part of phase I clinical trials (ClinicalTrials registration numbers NCT01506570 and NCT01436422) at the Johns Hopkins Bloomberg School of Public Health (JHSPH) and at the University of Vermont Vaccine Testing Center and Center for Immunization, as previously reported (15,41,42).…”

Section: Methodsmentioning

confidence: 99%

Prior Dengue Virus Exposure Shapes T Cell Immunity to Zika Virus in Humans

Grifoni

Pham

Sidney

et al. 2017

J Virol

Self Cite

155

214

View full text Add to dashboard Cite

While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here, we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether preexisting dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with tetravalent dengue attenuated vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors but declines in DENV-preexposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells from DENV-preexposed donors selectively upregulated granzyme B and PD1, unlike DENV-naive donors. Finally, we discovered that ZIKV

show abstract

Section: Methodsmentioning

confidence: 99%

Prior Dengue Virus Exposure Shapes T Cell Immunity to Zika Virus in Humans

Grifoni

Pham

Sidney

et al. 2017

J Virol

Self Cite

155

214

View full text Add to dashboard Cite

show abstract

“…As most vaccines do, dengue vaccines rely on antibodies to achieve protection (10). Strong evidence supports a role for neutralizing antibodies and the 50% neutralizing (PRNT 50 ) titer is widely adopted as a surrogate marker for vaccine efficacy (11)(12)(13). Although the presence of neutralizing antibodies may be associated with a lower risk of disease, a clear correlation between a defined level of neutralization and protection from any serotype remains to be established (14,15).…”

Section: Introductionmentioning

confidence: 99%

Dengue vaccine–induced CD8+ T cell immunity confers protection in the context of enhancing, interfering maternal antibodies

Lam

Chua²,

Lee

et al. 2017

JCI Insight

View full text Add to dashboard Cite

“…The Laboratory of Infectious Diseases (LID) of the NIH is developing a live-attenuated chimeric Zika virus vaccine based on one of the components of its live attenuated tetravalent dengue vaccine currently in Phase 3 clinical trial in Brazil. 37,38 The candidate Zika virus vaccine virus is comprised the prM and E proteins of Zika virus and the nonstructural proteins of the DENV-2. It is expected to begin Phase 1 clinical evaluation in Flavivirus-naïve subjects in the fourth quarter of 2016.…”

Section: Vaccine Platformsmentioning

confidence: 99%

Vaccine Development for Zika Virus—Timelines and Strategies

Durbin

2016

Semin Reprod Med

View full text Add to dashboard Cite

Zika virus is a mosquito-borne Flavivirus that spread rapidly through South and Central America in 2015 to 2016. Microcephaly has been causally associated with Zika virus infection during pregnancy and the World Health Organization declared Zika virus as a Public Health Emergency of International Concern. To address this crisis, many groups have expressed their commitment to developing a Zika virus vaccine. Different strategies for Zika virus vaccine development are being considered including recombinant live attenuated vaccines, purified inactivated vaccines (PIVs), DNA vaccines, and viral vectored vaccines. Important to Zika virus vaccine development will be the target group chosen for vaccination and which end point(s) is chosen for efficacy determination. The first clinical trials of Zika virus vaccine candidates will begin in Q3/4 2016 but the pathway to licensure for a Zika virus vaccine is expected to take several years. Efforts are ongoing to accelerate Zika virus vaccine development and evaluation with the ultimate goal of reducing time to licensure.

show abstract

Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults

Abstract: NCT01072786 and NCT01436422.

Cited by 165 publications

References 24 publications

Prior Dengue Virus Exposure Shapes T Cell Immunity to Zika Virus in Humans

Prior Dengue Virus Exposure Shapes T Cell Immunity to Zika Virus in Humans

Dengue vaccine–induced CD8+ T cell immunity confers protection in the context of enhancing, interfering maternal antibodies

Vaccine Development for Zika Virus—Timelines and Strategies

Contact Info

Product

Resources

About