Antigenicity and Immunogenicity of a Trimeric Envelope Protein from an Indian Clade C HIV-1 Isolate

Priya, Rangasamy Sneha; Mittal, Veena; Kalisz, Irene; Whitney, Stephen; Priyanka, Dhopeshwarkar; LaBranche, Celia C.; Teja, Mullapudi Sri; Montefiori, David C.; Pal, Ranajit; Mahalingam, Sundarasamy; Kalyanaraman, Vaniambadi S.

doi:10.1074/jbc.m114.621185

Cited by 10 publications

(12 citation statements)

References 66 publications

(52 reference statements)

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“…The trimers were purified to homogeneity by lectin-affinity, size-exclusion and anion-exchange chromatography. This envelope design has proven to be quite effective in eliciting functional and protective B-cell and antibody responses in animal models [32,34,[37][38][39]. Our results showed that uncleaved envelopes had strong affinity interactions with rhesus and human CD4 proteins, and clearly formed trimers, as was evident from the EGS crosslinking and subsequent SDS-PAGE analysis.…”

Section: Discussionsupporting

confidence: 55%

“…Four rabbits were immunized intramuscularly (IM) by electroporation three times with a mixture of DNA encoding SIVmac251 gp140 and SIVsmE660 gp145, followed by two IM boosts of a mixture of the trimeric homologous proteins formulated in Adjuplex adjuvant. Adjuplex adjuvant was selected for this evaluation as our earlier study has shown that this adjuvant was highly effective in eliciting a robust immune response in rabbits when used with HIV Env [32]. The antibody titres against the two homologous envelope proteins measured throughout the course of immunization are shown in Fig.…”

Section: Antigenic and Immunogenic Characterization Of Trimeric Siv Ementioning

confidence: 99%

“…Gibco 293 H cells (Thermo Fisher Scientific) were transfected with the above DNAs using Transfectamine 2000 (Invitrogen) as performed previously [32]. Envelope proteins were purified from conditioned media in a three-step purification process: affinity chromatography using Galanthus nivalis lectin (GNL) agarose beads (Vector Laboratories), anion-exchange chromatography using mono-Q sepharose beads (GE Healthcare) and a gel filtration step to selectively isolate trimeric protein.…”

Section: Envelope Proteinsmentioning

confidence: 99%

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DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and Advax delta inulin adjuvant

Mittal

Ayala

Rangaswamy

et al. 2017

Journal of General Virology

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The partial success of the RV144 trial underscores the importance of envelope-specific antibody responses for an effective HIV-1 vaccine. Oligomeric HIV-1 envelope proteins delivered with a potent adjuvant are expected to elicit strong antibody responses with broad neutralization specificity. To test this hypothesis, two SIV envelope proteins were formulated with delta inulin-based adjuvant (Advax) and used to immunize nonhuman primates. Oligomeric gp140-gp145 from SIVmac251 and SIVsmE660 was purified to homogeneity. Oligomers showed high-affinity interaction with CD4 and were highly immunogenic in rabbits, inducing Tier 2 SIV-neutralizing antibodies. The immunogenicity of an oligomeric Env DNA prime and protein boost together with Advax was evaluated in Chinese rhesus macaques. DNA administration elicited antibodies to both envelopes, and titres were markedly enhanced following homologous protein boosts via intranasal and intramuscular routes. Strong antibody responses were detected against the V1 and V2 domains of gp120. During peak immune responses, a low to moderate level of neutralizing activity was detected against Tier 1A/1B SIV isolates, with a moderate level noted against a Tier 2 isolate. Increased serum antibody affinity to SIVmac251 gp140 and generation of Env-specific memory B cells were observed in the immunized macaques. Animals were subjected to low-dose intravaginal challenge with SIVmac251 one week after the last protein boost. One out of three immunized animals was protected from infection. Although performed with a small number of macaques, this study demonstrates the utility of oligomeric envelopes formulated with Advax in eliciting broad antibody responses with the potential to provide protection against SIV transmission.

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Section: Discussionsupporting

confidence: 55%

Section: Antigenic and Immunogenic Characterization Of Trimeric Siv Ementioning

confidence: 99%

Section: Envelope Proteinsmentioning

confidence: 99%

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DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and Advax delta inulin adjuvant

Mittal

Ayala

Rangaswamy

et al. 2017

Journal of General Virology

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“…These findings indicate that the long-lasting antibody response may be strongly influenced by the use of rNDV vector as a prime. In addition, various reports have shown that multiple immunizations with protein immunogens are required to induce a long-term immune response to HIV Env protein in guinea pigs and rabbits (3,20,21). In one of these reports, Shu et al (3) showed that a single chimeric clade B Env (HxB2/Balgp140) protein immunization significantly boosted the antibody titer in guinea pigs primed with either DNA or recombinant adenovirus type 5 (rAd5) vaccine and attained a antibody titer similar to those achieved after three sequential protein immunizations.…”

Section: Figmentioning

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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“…The peptides were adsorbed onto 96-well ELISA immuno maxisorp plates (Thermo Fisher) at a concentration of 5 μg/ml in 100 mM NaHCO 3 , pH 9.6, by overnight incubation at 4 °C and ELISA was performed as described previously55 to map the epitope specificity of samples demonstrating good breadth and potency of neutralization. Each experiment was repeated three times.…”

Section: Methodsmentioning

confidence: 99%

Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals

Cheedarla

Precilla

Babu

et al. 2017

Sci Rep

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Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good breadth of neutralization (neutralized >90% of the viruses). Four of these samples neutralized even the difficult-to-neutralize tier-3 pseudoviruses with great potency (GMT > 600). Analysis of neutralization specificities indicated that four samples had antibodies with multiple epitope binding specificities, viz. CD4-binding site (CD4BS), glycans in the V1/V2 and V3 regions and membrane proximal external region (MPER). Our findings indicate the strong possibility of identifying highly potent bNAbs with known or novel specificities from HIV-1 subtype C infected individuals from India that can be exploited as therapeutic tools or lead molecules for the identification of potential epitopes for design of a protective HIV-1 vaccine.

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Antigenicity and Immunogenicity of a Trimeric Envelope Protein from an Indian Clade C HIV-1 Isolate

Cited by 10 publications

References 66 publications

DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and Advax delta inulin adjuvant

DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and Advax delta inulin adjuvant

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

Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals

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