Mucosal Immunization with Newcastle Disease Virus Vector Coexpressing HIV-1 Env and Gag Proteins Elicits Potent Serum, Mucosal, and Cellular Immune Responses That Protect against Vaccinia Virus Env and Gag Challenges

Khattar, Sunil K.; Manoharan, Vinoth K.; Bhattarai, Bikash; LaBranche, Celia C.; Montefiori, David C.; Samal, Siba K.

doi:10.1128/mbio.01005-15

Cited by 26 publications

(24 citation statements)

References 36 publications

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“…To evaluate the efficacy of antipoliovirus vaccination with the NDV-polio construct, we performed intranasal immunization of guinea pigs. Previous research indicates that the immune response of guinea pigs to NDV vector-based vaccines resembles that observed in primate models (31,38,39). Four animals in each group were immunized with either NDV-polio or the NDV vector without poliovirus inserts.…”

Section: Resultsmentioning

confidence: 99%

Newcastle Disease Virus-Based Vectored Vaccine against Poliomyelitis

Viktorova

Khattar

Kouiavskaia

et al. 2018

J Virol

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The poliovirus eradication initiative has spawned global immunization infrastructure and dramatically decreased the prevalence of the disease, yet the original virus eradication goal has not been met. The suboptimal properties of the existing vaccines are among the major reasons why the program has repeatedly missed eradication deadlines. Oral live poliovirus vaccine (OPV), while affordable and effective, occasionally causes the disease in the primary recipients, and the attenuated viruses rapidly regain virulence and can cause poliomyelitis outbreaks. Inactivated poliovirus vaccine (IPV) is safe but expensive and does not induce the mucosal immunity necessary to interrupt virus transmission. While the need for a better vaccine is widely recognized, current efforts are focused largely on improvements to the OPV or IPV, which are still beset by the fundamental drawbacks of the original products. Here we demonstrate a different design of an antipoliovirus vaccine based on production of virus-like particles (VLPs). The poliovirus capsid protein precursor, together with a protease required for its processing, are expressed from a Newcastle disease virus (NDV) vector, a negative-strand RNA virus with mucosal tropism. In this system, poliovirus VLPs are produced in the cells of vaccine recipients and are presented to their immune systems in the context of active replication of NDV, which serves as a natural adjuvant. Intranasal administration of the vectored vaccine to guinea pigs induced strong neutralizing systemic and mucosal antibody responses. Thus, the vectored poliovirus vaccine combines the affordability and efficiency of a live vaccine with absolute safety, since no full-length poliovirus genome is present at any stage of the vaccine life cycle. A new, safe, and effective vaccine against poliovirus is urgently needed not only to complete the eradication of the virus but also to be used in the future to prevent possible virus reemergence in a postpolio world. Currently, new formulations of the oral vaccine, as well as improvements to the inactivated vaccine, are being explored. In this study, we designed a viral vector with mucosal tropism that expresses poliovirus capsid proteins. Thus, poliovirus VLPs are produced , in the cells of a vaccine recipient, and are presented to the immune system in the context of vector virus replication, stimulating the development of systemic and mucosal immune responses. Such an approach allows the development of an affordable and safe vaccine that does not rely on the full-length poliovirus genome at any stage.

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Section: Resultsmentioning

confidence: 99%

Newcastle Disease Virus-Based Vectored Vaccine against Poliomyelitis

Viktorova

Khattar

Kouiavskaia

et al. 2018

J Virol

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“…Whereas the titer of Env-specific IgG in serum was sustained at the peak response level for at least 160 days, there was a marginal decline in the mucosal IgG titer in vaginal washes. Recently, we demonstrated that immunization of guinea pigs with rNDV expressing gp160 without any protein boost elicited long-lasting systemic and mucosal immune responses to HIV (14). These findings indicate that the long-lasting antibody response may be strongly influenced by the use of rNDV vector as a prime.…”

Section: Figmentioning

confidence: 97%

“…There is no preexisting immunity to NDV in humans. NDV infects via the intranasal and oral routes and induces both mucosal and systemic immune responses (9)(10)(11)(12)(13)(14)(15)(16)(17). Previously, we demonstrated the potential of NDV as a vaccine vector for HIV-1 (14)(15)(16)(17).…”

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confidence: 99%

Enhanced Immune Responses to HIV-1 Envelope Elicited by a Vaccine Regimen Consisting of Priming with Newcastle Disease Virus Expressing HIV gp160 and Boosting with gp120 and SOSIP gp140 Proteins

Khattar

DeVico

LaBranche

et al. 2016

J Virol

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dNewcastle disease virus (NDV) expressing HIV-1 BaL gp160 was evaluated either alone or with monomeric BaL gp120 and BaL SOSIP gp140 protein in a prime-boost combination in guinea pigs to enhance envelope (Env)-specific humoral and mucosal immune responses. We showed that a regimen consisting of an NDV prime followed by a protein boost elicited stronger serum and mucosal Th-1-biased IgG responses and neutralizing antibody responses than NDV-only immunizations. Additionally, these responses were higher after the gp120 than after the SOSIP gp140 protein boost. It is believed that an effective vaccine against HIV-1 should induce potent systemic and mucosal immune responses. Therefore, the use of live-virus vectored vaccines capable of replicating at mucosal surface has become very attractive. To induce robust antibody (Ab) responses, several of these vectored vaccines are being evaluated either alone or in several prime-boost combinations using different forms of HIV envelope (Env) protein (1-4). It has been reported that a viral vector prime and protein boost regiment could elicit protective immunity to HIV-1 in nonhuman primates (4-7) and, recently, in humans in an RV-144 vaccine trial (8). Among the different viral vector systems under evaluation for HIV, Newcastle disease virus (NDV), an avian paramyxovirus, has the characteristics desired for an HIV-1 vaccine. There is no preexisting immunity to NDV in humans. NDV infects via the intranasal and oral routes and induces both mucosal and systemic immune responses (9-17). Previously, we demonstrated the potential of NDV as a vaccine vector for HIV-1 (14-17). However, the concept of an NDV vector prime followed by Env protein boost to increase immune responses to HIV has never been evaluated previously.In order to identify an improved vaccination regimen that elicits a higher level of anti-HIV humoral as well as mucosal immune responses, an avirulent recombinant NDV (rNDV) strain, LaSota, expressing gp160 of HIV-1 strain BaL.1 was used as a prime followed by a boost with purified monomeric gp120 and trimeric SOSIP gp140 proteins in this study. The construction and characterization of rNDV expressing gp160 (rNDV-gp160) were described before (16). Briefly, the gp160 protein expressed by rNDV was detected on infected cell surfaces and was also incorporated into the NDV virion. Further, gp160 present in infected cells and in the virion formed oligomers which were recognized by conformationally dependent monoclonal Abs (MAbs). The BaL gp120 and SOSIP gp140 proteins (18) were produced as described previously (19). The BaL SOSIP gp140 protein has been characterized by Dey et al. (19), and they demonstrated that BaL SOSIP gp140, expressed in HEK 293 cells, was a mixture of monomers, dimers, and trimers. Guinea pigs were used to evaluate the humoral and mucosal immune responses induced by this vaccine regimen. Female Hartley guinea pigs obtained from Charles River Laboratories were assigned to four groups (n ϭ 3/group) as shown in Fig. 1. Each animal in all the groups recei...

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“…An exogene can be placed at the gene junction between any two genes of the virus, yet the 3 rd position has been found to be the most optimal for NDV vector [149,182,185,186] with the 1 st and the 2 nd ones being the least optimal [148,149]. NDV has been used for vectoring the antigens of RSV [185], AMPV [187][188][189], HIV [149,190,191], HPIV3 [182], influenza A virus [192], SARS-coronavirus [186], Nipah virus [193], and Ebola virus [194]. Examples of NDV vectoring pneumoviral antigens are reported in Table 4.…”

Section: Newcastle Disease Virusmentioning

confidence: 99%

Engineering of Live Chimeric Vaccines against Human Metapneumovirus

2020

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Human metapneumovirus (HMPV) is an important human pathogen that, along with respiratory syncytial virus (RSV), is a major cause of respiratory tract infections in young infants. Development of an effective vaccine against Pneumoviruses has proven to be particularly difficult; despite over 50 years of research in this field, no vaccine against HMPV or RSV is currently available. Recombinant chimeric viruses expressing antigens of other viruses can be generated by reverse genetics and used for simultaneous immunization against more than one pathogen. This approach can result in the development of promising vaccine candidates against HMPV, and several studies have indeed validated viral vectors expressing HMPV antigens. In this review, we summarize current efforts in generating recombinant chimeric vaccines against HMPV, and we discuss their potential optimization based on the correspondence with RSV studies.

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Mucosal Immunization with Newcastle Disease Virus Vector Coexpressing HIV-1 Env and Gag Proteins Elicits Potent Serum, Mucosal, and Cellular Immune Responses That Protect against Vaccinia Virus Env and Gag Challenges

Cited by 26 publications

References 36 publications

Newcastle Disease Virus-Based Vectored Vaccine against Poliomyelitis

Newcastle Disease Virus-Based Vectored Vaccine against Poliomyelitis

Enhanced Immune Responses to HIV-1 Envelope Elicited by a Vaccine Regimen Consisting of Priming with Newcastle Disease Virus Expressing HIV gp160 and Boosting with gp120 and SOSIP gp140 Proteins

Engineering of Live Chimeric Vaccines against Human Metapneumovirus

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