Viral vectors as vaccine platforms: deployment in sight

Rollier, Christine S.; Reyes-Sandoval, Arturo; Cottingham, Matthew G.; Ewer, Katie; Hill, Adrian V. S.

doi:10.1016/j.coi.2011.03.006

Cited by 187 publications

(179 citation statements)

References 41 publications

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“…Many successful vaccines are based on liveattenuated pathogens and usually confer strong and long-lasting immunity (32,33). Compared to inactivated vaccines, live viral vaccines are known to induce strong cellular immunity, which is important for combating various human diseases ranging from microbial infections to cancers.…”

Section: Discussionmentioning

confidence: 99%

A Novel Live Pichinde Virus-Based Vaccine Vector Induces Enhanced Humoral and Cellular Immunity after a Booster Dose

Dhanwani

Zhou

Huang

et al. 2016

J Virol

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Pichinde virus (PICV) is a bisegmented enveloped RNA virus that targets macrophages and dendritic cells (DCs) early in infection and induces strong innate and adaptive immunity in mice. We have developed a reverse genetics system to produce live recombinant PICV (strain P18) with a trisegmented RNA genome (rP18tri), which encodes all four PICV gene products and as many as two foreign genes. We have engineered the vector to express the green fluorescent protein (GFP) reporter gene (abbreviated as G in virus designations) and either the hemagglutination (HA [H]) or the nucleoprotein (NP [P]) gene of the influenza A/PR8 virus. The trisegmented viruses rP18tri-G/H and rP18tri-G/P showed slightly reduced growth in vitro and expressed HA and NP, respectively. Mice immunized with rP18tri-G/H were completely protected against lethal influenza virus challenge even 120 days after immunization. These rP18tri-based vectors could efficiently induce both neutralizing antibodies and antigen-specific T cell responses via different immunization routes. Interestingly, the immune responses were significantly increased upon a booster dose and remained at high levels even after three booster doses. In summary, we have developed a novel PICV-based live vaccine vector that can express foreign antigens to induce strong humoral and cell-mediated immunity and is ideal for a primeand-boost vaccination strategy. IMPORTANCE We have developed a novel Pichinde virus (PICV)-based live viral vector, rP18tri, that packages three RNA segments and encodes as many as two foreign genes. Using the influenza virus HA and NP genes as model antigens, we show that this rP18tri vector can induce strong humoral and cellular immunity via different immunization routes and can lead to protection in mice. Interestingly, a booster dose further enhances the immune responses, a feature that distinguishes this from other known live viral vectors. In summary, our study demonstrates a unique feature of this live rP18tri vector to be used as a novel vaccine platform for a prime-and-boost vaccination strategy.A renaviruses are enveloped RNA viruses with a bisegmented genome and mostly use rodents as natural hosts. There are at least 27 members that are geographically, serologically, and phylogenetically divided into Old World and New World arenaviruses (1). The prototypic lymphocytic choriomeningitis virus (LCMV) infection of mice has long been used as a valuable model with which to study viral persistence and virus-induced immunity and immunopathology (2, 3). The arenavirus is composed of a total of four genes on two genomic RNA segments in opposite orientations (1). The Z protein, produced from the large (L) genomic segment, is a small RING domain-containing matrix protein that mediates virus budding, regulates viral RNA synthesis, and mediates host immune suppression (4, 5). The large L protein (ϳ200 kDa), also encoded on the L segment, is the RNA-dependent RNA polymerase (RdRp), which is required for viral RNA synthesis (6). The glycoprotein (GPC), encoded...

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Section: Discussionmentioning

confidence: 99%

A Novel Live Pichinde Virus-Based Vaccine Vector Induces Enhanced Humoral and Cellular Immunity after a Booster Dose

Dhanwani

Zhou

Huang

et al. 2016

J Virol

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“…Thus, genomic treatment using NA as drugs is proposed as a therapeutic solution to treat several human diseases. In addition to the correction of transmitted or acquired genetic defects, this approach might be used for other applications including: (i) functional gene studies [1]; (ii) production of relevant proteins; or (iii) immunization against cancer cells and infectious pathogens [2]. In addition, RNA interference (RNAi) also offers many possibilities for gene delivery through the inhibition of genes particularly those implicated in cancer [3].…”

Section: Introductionmentioning

confidence: 99%

Synthetic vectors for gene delivery: An overview of their evolution depending on routes of administration.

Belmadi

Midoux

Loyer

et al. 2015

Biotechnology Journal

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Nucleic acid delivery constitutes an emerging therapeutic strategy to cure various human pathologies. This therapy consists of introducing genetic material into the whole body or isolated cells to correct a cellular abnormality or disfunction. As with any drug, the main objective of nucleic acid delivery is to establish optimal balance between efficacy and tolerance. The methods of administration and the vectors used are selected depending on whether the goal of treatment is the production of an active protein; the replacement of a missing or inactive gene; or the combat of acquired diseases, such as cancer or AIDS. In that sense, synthetic vectors represent a valuable solution because they are well characterized, their structure can be fine tuned, and their potential toxicity can be reduced, since toxicity depends on the composition of the formulations. Here we review various synthetic vectors for gene delivery and address the question of their biodistribution as a function of the route of administration. We highlight the modifications to vectors structure and formulations necessary to overcome the major hurdles limiting the effectiveness of nucleic acid therapies.

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“…However, the female cervicovaginal mucosa is generally considered a difficult site in which to induce an immune response (3), and, with the exception of replication-competent microbial vectors (which raise safety concerns; refs. 4,5), there is little evidence for effective vaccination via the female cervicovaginal mucosa (6,7). Efforts to induce genital CD8 + T cell responses have therefore focused on either systemic immunization or mucosal immunization at distant sites, particularly the upper respiratory tract.…”

Section: Introductionmentioning

confidence: 99%

Intravaginal immunization with HPV vectors induces tissue-resident CD8+ T cell responses

Çuburu¹,

Graham²,

Buck³

et al. 2012

J. Clin. Invest.

118

135

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Viral vectors as vaccine platforms: deployment in sight

Cited by 187 publications

References 41 publications

A Novel Live Pichinde Virus-Based Vaccine Vector Induces Enhanced Humoral and Cellular Immunity after a Booster Dose

A Novel Live Pichinde Virus-Based Vaccine Vector Induces Enhanced Humoral and Cellular Immunity after a Booster Dose

Synthetic vectors for gene delivery: An overview of their evolution depending on routes of administration.

Intravaginal immunization with HPV vectors induces tissue-resident CD8+ T cell responses

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