Recent Advances in Zika Virus Vaccines

Garg, Himanshu; Mehmetoglu-Gurbuz, Tugba; Joshi, Anjali

doi:10.3390/v10110631

Cited by 38 publications

(40 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A few drugs against ZIKV have also been proposed and may have an impact on testicles [106,120,121]. Recently, Z2 an amphipathic peptide derived from the stem region of ZIKV envelope protein was reported to inhibit vertical ZIKV transmission in a mouse model and reduce viral load in the testicle and epididymis.…”

Section: Zikv Vaccines and Treatment To Improve The Host Response In mentioning

confidence: 99%

The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology

Almeida

Braz-de-Melo

Santos

et al. 2020

Cells

View full text Add to dashboard Cite

Zika virus (ZIKV) has been reported by several groups as an important virus causing pathological damage in the male reproductive tract. ZIKV can infect and persist in testicular somatic and germ cells, as well as spermatozoa, leading to cell death and testicular atrophy. ZIKV has also been detected in semen samples from ZIKV-infected patients. This has huge implications for human reproduction. Global scientific efforts are being applied to understand the mechanisms related to arboviruses persistency, pathogenesis, and host cellular response to suggest a potential target to develop robust antiviral therapeutics and vaccines. Here, we discuss the cellular modulation of the immunologic and physiologic properties of the male reproductive tract environment caused by arboviruses infection, focusing on ZIKV. We also present an overview of the current vaccine effects and therapeutic targets against ZIKV infection that may impact the testis and male fertility.

show abstract

Section: Zikv Vaccines and Treatment To Improve The Host Response In mentioning

confidence: 99%

The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology

Almeida

Braz-de-Melo

Santos

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…No statistically significant differences (p = 0.336) in viral titers were observed using ANOVA test. of infection, mortality or detection of the virus at different times post-infection in the blood or organs of infected animals 33,45 . Thus, the use of IFNAR −/− A129 immunodeficient mice represented the best suitable model to demonstrate the successful rescue of recombinant ZIKV using in vivo reverse genetics.…”

Section: Discussionmentioning

confidence: 99%

“…DNA vaccines have several advantages over LAVs, including stability and cost 45,46 . However, DNA vaccines have been hampered by issues related to poor immunogenicity and/or the need for inoculation of high amounts (mgs) in order to generate adequate protective responses.…”

Section: Discussionmentioning

confidence: 99%

“…(2020) 10:512 | https://doi.org/10.1038/s41598-020-57545-2 www.nature.com/scientificreports www.nature.com/scientificreports/ The major drawback of LAVs is that they may require specialized culture system substrates for production and a cold-chain to maintain the integrity of the vaccine 45,47 . The ability to combine the advantages of these two systems, like the one described in this report, opens the exciting possibility for greatly improving vaccines and vaccination strategies for a myriad of pathogens, including ZIKV.…”

Section: Scientific Reports |mentioning

confidence: 99%

See 1 more Smart Citation

In vivo rescue of recombinant Zika virus from an infectious cDNA clone and its implications in vaccine development

Ávila‐Pérez

Nogales

Park

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Zika virus (ZiKV) is a mosquito-borne member of theFlaviviridae family that has been known to circulate for decades causing mild febrile illness. the more recent ZiKV outbreaks in the Americas and the caribbean associated with congenital malformations and Guillain-Barré syndrome in adults have placed public health officials in high alert and highlight the significant impact of ZIKV on human health. New technologies to study the biology of ZIKV and to develop more effective prevention options are highly desired. in this study we demonstrate that direct delivery in mice of an infectious ZiKV cDnA clone allows the rescue of recombinant (r)ZiKV in vivo. A bacterial artificial chromosome containing the sequence of ZIKV strain Paraiba/2015 under the control of the cytomegalovirus promoter was complexed with a commercial transfection reagent and administrated using different routes in type-I interferon receptor deficient A129 mice. Clinical signs and death associated with ZIKV viremia were observed in mice. the rZiKV recovered from these mice remained fully virulent in a second passage in mice. interestingly, infectious rZiKV was also recovered after intraperitoneal inoculation of the rZiKV cDnA in the absence of transfection reagent. further expanding these studies, we demonstrate that a single intraperitoneal inoculation of a cDnA clone encoding an attenuated rZiKV was safe, highly immunogenic, and provided full protection against lethal ZiKV challenge. this novel in vivo reverse genetics method is a potentially suitable delivery platform for the study of wild-type and liveattenuated ZiKV devoid of confounding factors typical associated with in vitro systems. Moreover, our results open the possibility of employing similar in vivo reverse genetic approaches for the generation of other viruses and, therefore, change the way we will use reverse genetics in the future.Zika virus (ZIKV), a member of the Flaviviridae family, became a global public concern because of the correlation of Zika virus epidemic with fetal developmental defects, including highly publicized cases of microcephaly 1 . The viral genome is made of a positive sense, single-stranded RNA molecule (~10.8 kb) that contains a single open reading frame flanked by 5′ and 3′ untranslated regions 2-4 . The viral RNA is translated as a single polyprotein that is co-and post-translationally processed by viral and cellular proteases into three major structural proteins (capsid, pre-membrane and envelope) involved in viral entry, fusion and assembly 5 , and seven non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) that are involved in viral RNA replication and transcription, assembly and evasion of the host antiviral responses [6][7][8][9] .Although the majority of ZIKV infections are asymptomatic or associated with a mild febrile illness, infection during pregnancy has been associated with miscarriage and severe congenital malformations, including fetal

show abstract

“…The DI-DII region of ZIKV E protein is a target for cross-reactive antibodies with other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), whereas the DIII domain induces ZIKV-specific antibodies [10][11][12], and therefore, is a key target for ZIKV vaccine development. ZIKV vaccine candidates under development include inactivated virus, live attenuated virus, DNA, mRNA, viral vectors, virus-like particles (VLPs), and viral proteins (or subunit vaccines) [13][14][15][16]. Although many have advanced clinical trials and been tested for immunogenicity and/or levels of protection [17][18][19], none are approved for use in humans.…”

mentioning

confidence: 99%

Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine

et al. 2019

View full text Add to dashboard Cite

Zika virus (ZIKV), a mosquito-borne flavivirus, has attracted global attention due to its close association with congenital Zika syndrome and neurological diseases, and transmission through additional routes, such as sexual contact. Currently there are no vaccines approved for ZIKV, and thus, there is an urgent need to develop an effective and safe ZIKV vaccine. Domain III (DIII) of the ZIKV envelope (E) protein is an important vaccine target, and a vaccine developed using a mutant DIII of E (EDIII) protein protects adult and pregnant mice, and unborn offspring, against ZIKV infection. Here, we have used immunocompetent BALB/c mice treated with anti-interferon-α/β receptor 1 (Ifnar1) antibodies to investigate whether three adjuvants (aluminum (Alum), monophosphoryl lipid A (MPL), and MF59), either alone or in combination, could improve the efficacy of this EDIII subunit vaccine. Our data show that, although vaccine formulated with a single adjuvant induced a specific antibody and cellular immune response, and reduced viral load in mice challenged with ZIKV, the combination of Alum and MPL adjuvants led to a more robust and balanced immune response, stronger neutralizing activity against three recent ZIKV human strains, and greater protection against a high-dose ZIKV challenge. Particularly, the combination of Alum with MPL significantly reduced viral titers and viral RNA copy numbers in sera and tissues, including the male reproductive organs. Overall, this study has identified the combination of Alum and MPL as the most effective adjuvant for ZIKV EDIII subunit vaccines, and it has important implications for subunit vaccines against other enveloped viruses, including non-ZIKV flaviviruses.Vaccines 2019, 7, 161 2 of 16 with microcephaly, fetal demise, and other congenital disorders [4][5][6]. Thus, ZIKV has emerged as a global health threat and there is an urgent requirement for an effective vaccine to combat ZIKV-associated diseases.The ZIKV genome encodes a single polyprotein, which is processed into three structural proteins (capsid (C), precursor of membrane/membrane (prM/M), and envelope (E)) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [7][8][9]. The E protein has important roles in infection and pathogenesis, is involved in virus binding to target cells and membrane fusion, and also serves as an important vaccine target [7,8]. The E protein is a transmembrane protein and consists of three domains termed I, II, and III (DI-DIII), a fusion loop (FL), and a stalk region (S) [8]. The DI-DII region of ZIKV E protein is a target for cross-reactive antibodies with other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), whereas the DIII domain induces ZIKV-specific antibodies [10][11][12], and therefore, is a key target for ZIKV vaccine development. ZIKV vaccine candidates under development include inactivated virus, live attenuated virus, DNA, mRNA, viral vectors, virus-like particles (VLPs), and viral proteins (or subunit vaccines) [13][14][15][16]. Although ma...

show abstract

Recent Advances in Zika Virus Vaccines

Cited by 38 publications

References 75 publications

The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology

The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology

In vivo rescue of recombinant Zika virus from an infectious cDNA clone and its implications in vaccine development

Effects of Adjuvants on the Immunogenicity and Efficacy of a Zika Virus Envelope Domain III Subunit Vaccine

Contact Info

Product

Resources

About