Recombinant fowlpox virus vector-based vaccines: expression kinetics, dissemination and safety profile following intranasal delivery

Townsend, David G; Trivedi, Shubhanshi; Jackson, Ron; Ranasinghe, Charani

doi:10.1099/jgv.0.000702

Cited by 11 publications

(7 citation statements)

References 52 publications

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“…In summary, systemic rFWPV immunization probably elicited a faster innate immune response than systemic rAd immunization. Our observations are supported by a report that transgenes are already expressed in vivo 6 h after rFWPV vaccination (65). Moreover, similar to our results, other studies showed that Ad5 in general evokes relatively low innate immune responses compared to other adenoviruses (66,67), probably because Ad5 migrates into the nucleus relatively quickly (68).…”

Section: Discussionsupporting

confidence: 92%

Vector Order Determines Protection against Pathogenic Simian Immunodeficiency Virus Infection in a Triple-Component Vaccine by Balancing CD4 ⁺ and CD8 ⁺ T-Cell Responses

Sauermann

Radaelli

Stolte-Leeb

et al. 2017

J Virol

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An effective AIDS vaccine should elicit strong humoral and cellular immune responses while maintaining low levels of CD4 T cell activation to avoid the generation of target cells for viral infection. The present study investigated two prime-boost regimens, both starting vaccination with single cycle immunodeficiency virus, followed by two mucosal boosts either with recombinant adenovirus (rAd) or fowlpox virus (rFWPV) expressing SIVmac239 or SIVmac251 and genes, respectively. Finally, vectors were switched and systemically administered to the reciprocal group of animals. Only mucosal rFWPV immunizations followed by systemic rAd boost significantly protected animals against a repeated low-dose, intrarectal challenge with pathogenic SIVmac251 resulting in a vaccine efficacy (i.e. risk reduction per exposure) of 68%. Delayed viral acquisition was associated with higher levels of activated CD8 T cells and Gag-specific IFN-γ secreting CD8 cells, low virus-specific CD4 T cell responses and low Env antibody titers. In contrast, the systemic rFWPV boost induced strong virus-specific CD4 T cell activity. rAd and rFWPV also induced differential patterns of the innate immune responses, thereby possibly shaping the specific immunity. Plasma levels after final immunization correlated directly with virus-specific CD4 T cell responses and inversely with the number of exposures to infection. Also, the percentage of activated CD69 CD8 T cells correlated with the number of exposures to infection. Differential stimulation of the immune response likely provided the basis for the diverging levels of protection afforded by this vaccine regimen. A failed phase II AIDS vaccine trial led to the hypothesis that CD4 T cell activation can abrogate any potentially protective effects delivered by vaccination or promote acquisition of the virus because CD4 T helper cells, required for an effective immune response, also represent the target cells for viral infection. We compared two vaccination protocols that elicited similar levels of Gag-specific immune responses in rhesus macaques. Only the animal group that had a low level of virus-specific CD4 T cells in combination with high levels of activated CD8 T cells was significantly protected from infection. Notably, protection was achieved despite the lack of appreciable Env-antibody titers. Moreover, we show that both, the vector and the route of immunization affected the level of CD4 T cell responses. Thus, mucosal immunization with FWPV-based vaccines should be considered as potent prime in prime-boost vaccination protocols.

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Section: Discussionsupporting

confidence: 92%

Vector Order Determines Protection against Pathogenic Simian Immunodeficiency Virus Infection in a Triple-Component Vaccine by Balancing CD4 ⁺ and CD8 ⁺ T-Cell Responses

Sauermann

Radaelli

Stolte-Leeb

et al. 2017

J Virol

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“…booster with recombinant vaccinia virus (rVV) or rMVA expressing HIV antigens, induced sustained mucosal and systemic HIV-specific CD8 + T cell immunity 27,38 . rFPV was a useful intranasal priming delivery vector 27,37,39 and does not cross the olfactory receptor neuron pathway 40 , similar to what has been reported with rMVA 23 . Our studies also led to the discovery that IL-13 plays a crucial role in modulating T cell avidity in a route dependent manner, where mucosal vaccination induced high avidity T cells with improved efficacy by lowering innate lymphoid cells type 2-driven IL-13 expression at the vaccination site 41 and T cell driven IL-13 at the adaptive immune level 28,42,43 .…”

Section: Introductionsupporting

confidence: 75%

Mucosal and systemic SIV-specific cytotoxic CD4+ T cell hierarchy in protection following intranasal/intramuscular recombinant pox-viral vaccination of pigtail macaques

Khanna

Jackson

Alcântara

et al. 2019

Sci Rep

Self Cite

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A HIV vaccine that provides mucosal immunity is urgently needed. We evaluated an intranasal recombinant Fowlpox virus (rFPV) priming vaccine followed by intramuscular Modified Vaccinia Ankara (rMVA) booster vaccine, both expressing SIV antigens. The vaccination generated mucosal and systemic SIV-specific CD4 + T cell mediated immunity and was associated with partial protection against high-dose intrarectal SIV mac251 challenge in outbred pigtail macaques. Three of 12 vaccinees were completely protected and these animals elicited sustained Gag-specific poly-functional, cytotoxic mucosal CD4 + T cells, complemented by systemic poly-functional CD4 + and CD8 + T cell immunity. Humoral immune responses, albeit absent in completely protected macaques, were associated with partial control of viremia in animals with relatively weaker mucosal/systemic T cell responses. Co-expression of an IL-4R antagonist by the rFPV vaccine further enhanced the breadth and cytotoxicity/poly-functionality of mucosal vaccine-specific CD4 + T cells. Moreover, a single FPV- gag/pol/env prime was able to induce rapid anamnestic gp140 antibody response upon SIV encounter. Collectively, our data indicated that nasal vaccination was effective at inducing robust cervico-vaginal and rectal immunity, although cytotoxic CD4 + T cell mediated mucosal and systemic immunity correlated strongly with ‘complete protection’, the different degrees of protection observed was multi-factorial.

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“…The mismatch of the antigenicity between the "old" vaccines and the currently circulating pathogens has frankly compromised the vaccine protective efficacy. To overcome the problem associated with this mismatch, researchers have developed viral vectors such as turkey herpesvirus, NDV, and fowlpox virus (Bublot et al, 2006;Esaki et al, 2013;Townsend et al, 2017;Kim and Samal, 2018) to deliver antigens that can match with the variants of currently circulating pathogens. Among these vectors, NDV has been demonstrated to be one of the most promising candidates for developing multivalent poultry vaccines (Dimitrov et al, 2017;Kim and Samal, 2018).…”

Section: Discussionmentioning

confidence: 99%

Expression of Two Foreign Genes by a Newcastle Disease Virus Vector From the Optimal Insertion Sites through a Combination of the ITU and IRES-Dependent Expression Approaches

Zhang

2020

Front. Microbiol.

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Many Newcastle disease virus (NDV) strains have been developed as vectors to express a foreign gene (FG) for vaccine and cancer therapy purposes. The non-coding region between the phosphoprotein (P) and matrix protein (M) genes and the non-coding region behind the NP gene open reading frame (ORF) in the NDV genome have been identified as the optimal insertion sites for efficient FG expression through the independent transcription unit (ITU) and the internal ribosomal entry site (IRES) dependent expression approaches, respectively. To date, however, the majority of these NDV vectors express only a single or two FGs from suboptimal insertion sites in the NDV genome, obtaining various levels of FG expression. To improve the FG expression, we generated NDV LaSota vaccine strain-based recombinant viruses expressing two FGs, GFP, and RFP, from the identified optimal insertion sites through a combination of the ITU and IRESdependent approaches. Biological assessments of the recombinant viruses indicated that the recombinants expressing two FGs were slightly attenuated with approximately one order of magnitude lower in virus titers when compared to the viruses containing a single FG. The FG expression efficiencies from the two-FG viruses were also lower than those from the single-FG viruses. However, the expression of two FGs from the optimal insertion sites was significantly (p < 0.05) higher than those from the suboptimal insertion sites. The expressions of FGs as monocistronic ITU were approximately 4-fold more efficient than those expressed by the bicistronic IRES-dependent approach. These results suggest that the NDV LaSota vector could efficiently express two FGs from the identified optimal insertions sites. The ITU strategy could be used for "vectoring" FGs in circumstances where high expression of gene products (e.g., antigens) is warranted, whereas, the IRES-dependent tactic might be useful when lower amounts of IRES-directed FG products are needed.

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Recombinant fowlpox virus vector-based vaccines: expression kinetics, dissemination and safety profile following intranasal delivery

Cited by 11 publications

References 52 publications

Vector Order Determines Protection against Pathogenic Simian Immunodeficiency Virus Infection in a Triple-Component Vaccine by Balancing CD4 ⁺ and CD8 ⁺ T-Cell Responses

Vector Order Determines Protection against Pathogenic Simian Immunodeficiency Virus Infection in a Triple-Component Vaccine by Balancing CD4 ⁺ and CD8 ⁺ T-Cell Responses

Mucosal and systemic SIV-specific cytotoxic CD4+ T cell hierarchy in protection following intranasal/intramuscular recombinant pox-viral vaccination of pigtail macaques

Expression of Two Foreign Genes by a Newcastle Disease Virus Vector From the Optimal Insertion Sites through a Combination of the ITU and IRES-Dependent Expression Approaches

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Recombinant fowlpox virus vector-based vaccines: expression kinetics, dissemination and safety profile following intranasal delivery

Cited by 11 publications

References 52 publications

Vector Order Determines Protection against Pathogenic Simian Immunodeficiency Virus Infection in a Triple-Component Vaccine by Balancing CD4 + and CD8 + T-Cell Responses

Vector Order Determines Protection against Pathogenic Simian Immunodeficiency Virus Infection in a Triple-Component Vaccine by Balancing CD4 + and CD8 + T-Cell Responses

Mucosal and systemic SIV-specific cytotoxic CD4+ T cell hierarchy in protection following intranasal/intramuscular recombinant pox-viral vaccination of pigtail macaques

Expression of Two Foreign Genes by a Newcastle Disease Virus Vector From the Optimal Insertion Sites through a Combination of the ITU and IRES-Dependent Expression Approaches

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Vector Order Determines Protection against Pathogenic Simian Immunodeficiency Virus Infection in a Triple-Component Vaccine by Balancing CD4 ⁺ and CD8 ⁺ T-Cell Responses

Vector Order Determines Protection against Pathogenic Simian Immunodeficiency Virus Infection in a Triple-Component Vaccine by Balancing CD4 ⁺ and CD8 ⁺ T-Cell Responses