Evaluation of HIV-1 Regulatory and Structural Proteins as Antigen Candidate in Mice and Humans

Author(s): Narges Farahani Khojasteh, Mehrshad Fekri, Samaneh Hemmati Shabani, Alireza Milani, Kazem Baesi, Azam Bolhassani*

Journal Name: Current HIV Research
HIV and Viral Immune Diseases

Volume 19 , Issue 3 , 2021


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: The diagnosis of HIV infection is important among different groups. Moreover, combination antiretroviral therapy is used to treat HIV-1, but it cannot eradicate the infection. Thus, the development of therapeutic vaccines, along with antiretroviral therapy, is recommended. This study evaluates the values of four HIV proteins as antigen candidates in therapeutic vaccine design as well as a possible diagnostic marker for HIV infection in humans.

Methods: In this study, the HIV-1 Tat and Rev regulatory proteins and structural Gp120 and p24 proteins were generated in E. coli expression system. Their immunogenicity was evaluated in BALB/ c mice using homologous and heterologous prime/boost strategies. Moreover, the detection of anti- HIV IgG antibodies against these recombinant proteins was assessed in untreated (Naïve/ HIV-infected), treated, and drug-resistant patients compared to the healthy (control) group as a possible diagnostic marker for HIV infection.

Results: In humans, our results showed that among HIV-1 proteins, anti-Gp120 antibody was not detected in treated individuals compared to the healthy (control) group. The levels of anti-Gp120 antibody were significantly different between the treated group and Naïve as well as drug-resistant subjects. Moreover, the level of anti-p24 antibody was significantly lower in the treated group than the Naive group. In mice, the results of immunization indicated that the Rev antigen could significantly induce IgG2a, IgG2b, and IFN-γ secretion aimed at Th1 response as well as Granzyme B generation as CTL activity in comparison with other antigens. Furthermore, the heterologous DNA prime/ protein boost regimen was more potent than the homologous regimen for stimulation of cellular immunity.

Conclusion: Briefly, the levels of both anti-Gp120 and anti-p24 antibodies can be considered for the diagnosis of the HIV-infected individuals in different groups compared to the healthy group. Moreover, among four recombinant proteins, Rev elicited Th1 cellular immunity and CTL activity in mice as an antigen candidate in therapeutic vaccine development.

Keywords: HIV-1, regulatory protein, structural protein, drug resistance, immune responses, diagnosis.

[1]
Arya S, Lal P, Singh P, Kumar A. Recent advances in diagnosis of HIV and future prospects. Indian J Biotechnol 2015; 14: 9-18.
[2]
Pitt J, Henrard D, FitzGerald G, et al. Human immunodeficiency virus (HIV) type 1 antibodies in perinatal HIV-1 infection: association with human HIV-1 transmission, infection, and disease progression. For the Women and Infants Transmission Study. J Infect Dis 2000; 182(4): 1243-6.
[http://dx.doi.org/10.1086/315809] [PMID: 10979926]
[3]
Alexander TS. Human immunodeficiency virus diagnostic testing: 30 years of evolution. Clin Vaccine Immunol 2016; 23(4): 249-53.
[http://dx.doi.org/10.1128/CVI.00053-16] [PMID: 26936099]
[4]
Speers D, Phillips P, Dyer J. Combination assay detecting both human immunodeficiency virus (HIV) p24 antigen and anti-HIV antibodies opens a second diagnostic window. J Clin Microbiol 2005; 43(10): 5397-9.
[http://dx.doi.org/10.1128/JCM.43.10.5397-5399.2005] [PMID: 16208030]
[5]
Moore JP, Cao Y, Ho DD, Koup RA. Development of the anti-gp120 antibody response during seroconversion to human immunodeficiency virus type 1. J Virol 1994; 68(8): 5142-55.
[http://dx.doi.org/10.1128/JVI.68.8.5142-5155.1994] [PMID: 8035514]
[6]
Praharaj AK. Problems in diagnosis of HIV infection in babies. Med J Armed Forces India 2006; 62(4): 363-6.
[http://dx.doi.org/10.1016/S0377-1237(06)80110-3] [PMID: 27688543]
[7]
Li CC, Seidel KD, Coombs RW, Frenkel LM. Detection and quantification of human immunodeficiency virus type 1 p24 antigen in dried whole blood and plasma on filter paper stored under various conditions. J Clin Microbiol 2005; 43(8): 3901-5.
[http://dx.doi.org/10.1128/JCM.43.8.3901-3905.2005] [PMID: 16081929]
[8]
Bayon E, Morlieras J, Dereuddre-Bosquet N, et al. Overcoming immunogenicity issues of HIV p24 antigen by the use of innovative nanostructured lipid carriers as delivery systems: evidences in mice and non-human primates. NPJ Vaccines 2018; 3: 46.
[http://dx.doi.org/10.1038/s41541-018-0086-0] [PMID: 30302284]
[9]
Nabel GJ, Kwong PD, Mascola JR. Progress in the rational design of an AIDS vaccine. Philos Trans R Soc Lond B Biol Sci 2011; 366(1579): 2759-65.
[http://dx.doi.org/10.1098/rstb.2011.0096] [PMID: 21893538]
[10]
Tavernarakis N, Triantafyllaki A, Hatzakis A, Krambovitis E. Detection of anti-Rev antibodies in human immunodeficiency virus type-1 patients using a recombinant 18 kD Rev proein. Serodiagn Immunother Infect Disease 1993; 5: 117-21.
[http://dx.doi.org/10.1016/0888-0786(93)90052-2]
[11]
Bråve A, Ljungberg K, Boberg A, et al. Multigene/multisubtype HIV-1 vaccine induces potent cellular and humoral immune responses by needle-free intradermal delivery. Mol Ther 2005; 12(6): 1197-205.
[http://dx.doi.org/10.1016/j.ymthe.2005.06.473] [PMID: 16112909]
[12]
Bayer P, Kraft M, Ejchart A, Westendorp M, Frank R, Rösch P. Structural studies of HIV-1 Tat protein. J Mol Biol 1995; 247(4): 529-35.
[http://dx.doi.org/10.1016/S0022-2836(05)80133-0] [PMID: 7723010]
[13]
Ensoli B, Fiorelli V, Ensoli F, et al. Candidate HIV-1 Tat vaccine development: from basic science to clinical trials. AIDS 2006; 20(18): 2245-61.
[http://dx.doi.org/10.1097/QAD.0b013e3280112cd1] [PMID: 17117011]
[14]
Ensoli B, Nchabeleng M, Ensoli F, et al. HIV-Tat immunization induces cross-clade neutralizing antibodies and CD4(+) T cell increases in antiretroviral-treated South African volunteers: a randomized phase II clinical trial. Retrovirology 2016; 13(1): 34.
[http://dx.doi.org/10.1186/s12977-016-0261-1] [PMID: 27277839]
[15]
Hel Z, Johnson JM, Tryniszewska E, et al. A novel chimeric Rev, Tat, and Nef (Retanef) antigen as a component of an SIV/HIV vaccine. Vaccine 2002; 20(25-26): 3171-86.
[http://dx.doi.org/10.1016/S0264-410X(02)00258-X] [PMID: 12163269]
[16]
Verrier B, Le Grand R, Ataman-Önal Y, et al. Evaluation in rhesus macaques of Tat and rev-targeted immunization as a preventive vaccine against mucosal challenge with SHIV-BX08. DNA Cell Biol 2002; 21(9): 653-8.
[http://dx.doi.org/10.1089/104454902760330183] [PMID: 12396607]
[17]
Nicoli F, Finessi V, Sicurella M, et al. The HIV-1 Tat protein induces the activation of CD8+ T cells and affects in vivo the magnitude and kinetics of antiviral responses. PLoS One 2013; 8(11): e77746.
[http://dx.doi.org/10.1371/journal.pone.0077746] [PMID: 24223723]
[18]
Morettia S, Cafaroa A, Tripicianoa A, et al. HIV therapeutic vaccines aimed at intensifying combination antiretroviral therapy. Expert Rev Vaccines 2020; 19(1): 1-15.
[http://dx.doi.org/10.1080/14760584.2020.1712199] [PMID: 31971036]
[19]
Cafaro A, Tripiciano A, Picconi O, et al. Anti-tat immunity in HIV-1 infection: Effects of naturally occurring and vaccine-induced antibodies against Tat on the course of the disease. Vaccines (Basel) 2019; 7(3): 99.
[http://dx.doi.org/10.3390/vaccines7030099] [PMID: 31454973]
[20]
Liu Y, Li F, Qi Z, et al. The effects of HIV Tat DNA on regulating the immune response of HIV DNA vaccine in mice. Virol J 2013; 10: 297.
[http://dx.doi.org/10.1186/1743-422X-10-297] [PMID: 24073803]
[21]
Tomusange K, Wijesundara D, Gummow J, et al. A HIV- Tat/C4-binding protein chimera encoded by a DNA vaccine is highly immunogenic and contains acute EcoHIV infection in mice. Sci Rep 2016; 6: 29131.
[http://dx.doi.org/10.1038/srep29131] [PMID: 27358023]
[22]
Baesi K, Moallemi S, Ravanshad M. Phylogenetic analysis of HIV-1 pol gene: first subgenomic evidence of CRF29-BF among Iranian HIV-1 patients. Asian Pac J Trop Dis 2014; 4(2): S617-20.
[http://dx.doi.org/10.1016/S2222-1808(14)60690-3]
[23]
Baesi K, Ravanshad M, Ghanbarisafari M, Saberfar E, Seyedalinaghi S, Volk JE. Antiretroviral drug resistance among antiretroviral-naïve and treatment experienced patients infected with HIV in Iran. J Med Virol 2014; 86(7): 1093-8.
[http://dx.doi.org/10.1002/jmv.23898] [PMID: 24740443]
[24]
Ramezani A, Aghakhani A, Soleymani S, Bavand A, Bolhassani A. Significance of serum antibodies against HPV E7, Hsp27, Hsp20 and Hp91 in Iranian HPV-exposed women. BMC Infect Dis 2019; 19(1): 142.
[http://dx.doi.org/10.1186/s12879-019-3780-2] [PMID: 30755156]
[25]
Davoodi S, Bolhassani A, Sadat SM, Irani S. Enhancing HIV-1 Nef penetration into mammalian cells as an antigen candidate. JOMMID 2019; 7(1): 37-43.
[http://dx.doi.org/10.29252/JoMMID.7.1.2.37]
[26]
Namazi F, Bolhassani A, Sadat SM, Irani S. Histidine-rich nona-arginine and Latarcin 1 peptide successfully deliver HIV-1 Nef antigen in vitro. JOMMID 2019; 7(4): 107-15.
[http://dx.doi.org/10.29252/JoMMID.7.4.107]
[27]
Bolhassani A, Zahedifard F, Taghikhani M, Rafati S. Enhanced immunogenicity of HPV16E7 accompanied by Gp96 as an adjuvant in two vaccination strategies. Vaccine 2008; 26(26): 3362-70.
[http://dx.doi.org/10.1016/j.vaccine.2008.03.082] [PMID: 18471945]
[28]
Alizadeh S, Irani S, Bolhassani A, Sadat SM. Simultaneous use of natural adjuvants and cell penetrating peptides improves HCV NS3 antigen-specific immune responses. Immunol Lett 2019; 212: 70-80.
[http://dx.doi.org/10.1016/j.imlet.2019.06.011] [PMID: 31254535]
[29]
Kardani K, Hashemi A, Bolhassani A. Comparison of HIV-1 Vif and Vpu accessory proteins for delivery of polyepitope constructs harboring Nef, Gp160 and P24 using various cell penetrating peptides. PLoS One 2019; 14(10): e0223844.
[http://dx.doi.org/10.1371/journal.pone.0223844] [PMID: 31671105]
[30]
Daifalla NS, Bayih AG, Gedamu L. Differential immune response against recombinant leishmania donovani peroxidoxin 1 and peroxidoxin 2 proteins in BALB/c mice. J Immunol Res 2015; 2015: 348401.
[http://dx.doi.org/10.1155/2015/348401] [PMID: 26380320]
[31]
Doria-Rose NA, Haigwood NL. DNA vaccine strategies: candidates for immune modulation and immunization regimens. Methods 2003; 31(3): 207-16.
[http://dx.doi.org/10.1016/S1046-2023(03)00135-X] [PMID: 14511953]
[32]
Tindle RW, Croft S, Herd K, et al. A vaccine conjugate of ‘ISCAR’ immunocarrier and peptide epitopes of the E7 cervical cancer-associated protein of human papillomavirus type 16 elicits specific Th1- and Th2-type responses in immunized mice in the absence of oil-based adjuvants. Clin Exp Immunol 1995; 101(2): 265-71.
[http://dx.doi.org/10.1111/j.1365-2249.1995.tb08349.x] [PMID: 7544248]
[33]
Cicala C, Nawaz F, Jelicic K, Arthos J, Fauci AS. S Fauci A. HIV-1 gp120: a target for therapeutics and vaccine design. Curr Drug Targets 2016; 17(1): 122-35.
[http://dx.doi.org/10.2174/1389450116666150825120735] [PMID: 26302793]
[34]
Barouch DH, Santra S, Tenner-Racz K, et al. Potent CD4+ T cell responses elicited by a bicistronic HIV-1 DNA vaccine expressing gp120 and GM-CSF. J Immunol 2002; 168(2): 562-8.
[http://dx.doi.org/10.4049/jimmunol.168.2.562] [PMID: 11777947]
[35]
Filice G, Soldini L, Orsolini P, et al. Sensitivity and specificity of anti-HIV ELISA employing recombinant (p24, p66, gp120) and synthetic (gp41) viral antigenic peptides. Microbiologica 1991; 14(3): 185-94.
[PMID: 1717811]
[36]
Allain JP, Laurian Y, Einstein MH, et al. Monitoring of specific antibodies to human immunodeficiency virus structural proteins: clinical significance. Blood 1991; 77(5): 1118-23.
[http://dx.doi.org/10.1182/blood.V77.5.1118.1118] [PMID: 1671648]
[37]
Rychert J, Strick D, Bazner S, Robinson J, Rosenberg E. Detection of HIV gp120 in plasma during early HIV infection is associated with increased proinflammatory and immunoregulatory cytokines. AIDS Res Hum Retroviruses 2010; 26(10): 1139-45.
[http://dx.doi.org/10.1089/aid.2009.0290] [PMID: 20722464]
[38]
Re MC, Vignoli M, Furlini G, et al. Antibodies against full-length Tat protein and some low-molecular-weight Tat-peptides correlate with low or undetectable viral load in HIV-1 seropositive patients. J Clin Virol 2001; 21(1): 81-9.
[http://dx.doi.org/10.1016/S1386-6532(00)00189-X] [PMID: 11255101]
[39]
Rodriguez SK, Sarr AD, Olorunnipa O, et al. The absence of anti- Tat antibodies is associated with risk of disease progression in HIV-2 infection. J Infect Dis 2006; 194(6): 760-3.
[http://dx.doi.org/10.1086/507042] [PMID: 16941341]
[40]
Chen Q, Li L, Liao W, et al. Characterization of Tat antibody responses in Chinese individuals infected with HIV-1. PLoS One 2013; 8(4): e60825.
[http://dx.doi.org/10.1371/journal.pone.0060825] [PMID: 23565278]
[41]
Kjerrström A, Hinkula J, Engström G, et al. Interactions of single and combined human immunodeficiency virus type 1 (HIV-1) DNA vaccines. Virology 2001; 284(1): 46-61.
[http://dx.doi.org/10.1006/viro.2001.0905] [PMID: 11352667]
[42]
Tähtinen M, Strengell M, Collings A, et al. DNA vaccination in mice using HIV-1 nef, rev and tat genes in self-replicating pBN-vector. Vaccine 2001; 19(15-16): 2039-47.
[http://dx.doi.org/10.1016/S0264-410X(00)00420-5] [PMID: 11228375]
[43]
Addo MM, Altfeld M, Rosenberg ES, et al. The HIV-1 regulatory proteins Tat and Rev are frequently targeted by cytotoxic T lymphocytes derived from HIV-1-infected individuals. Proc Natl Acad Sci USA 2001; 98(4): 1781-6.
[http://dx.doi.org/10.1073/pnas.98.4.1781] [PMID: 11172028]
[44]
Okuda K, Bukawa H, Hamajima K, et al. Induction of potent humoral and cell-mediated immune responses following direct injection of DNA encoding the HIV type 1 env and rev gene products. AIDS Res Hum Retroviruses 1995; 11(8): 933-43.
[http://dx.doi.org/10.1089/aid.1995.11.933] [PMID: 7492440]
[45]
Stahl-Hennig C. Vaccination of seronegative volunteers with a human immunodeficiency virus type 1 env/rev DNA vaccine induces antigen-specific proliferation and lymphocyte production of B-chemokines. Proc Nat Acq Sc USA 2000; 97: 3388.
[46]
Cafaro A, Caputo A, Fracasso C, et al. Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine. Nat Med 1999; 5(6): 643-50.
[http://dx.doi.org/10.1038/9488] [PMID: 10371502]
[47]
Cafaro A, Titti F, Fracasso C, et al. Vaccination with DNA containing tat coding sequences and unmethylated CpG motifs protects cynomolgus monkeys upon infection with simian/human immunodeficiency virus (SHIV89.6P). Vaccine 2001; 19(20-22): 2862-77.
[http://dx.doi.org/10.1016/S0264-410X(01)00002-0] [PMID: 11282197]
[48]
Cui Z, Patel J, Tuzova M, et al. Strong T cell type-1 immune responses to HIV-1 Tat (1-72) protein-coated nanoparticles. Vaccine 2004; 22(20): 2631-40.
[http://dx.doi.org/10.1016/j.vaccine.2003.12.013] [PMID: 15193389]
[49]
Trivedi S, Jackson RJ, Ranasinghe C. Different HIV pox viral vector-based vaccines and adjuvants can induce unique antigen presenting cells that modulate CD8 T cell avidity. Virology 2014; 468-470: 479-89.
[http://dx.doi.org/10.1016/j.virol.2014.09.004] [PMID: 25261870]
[50]
Borsutzky S, Fiorelli V, Ebensen T, et al. Efficient mucosal delivery of the HIV-1 Tat protein using the synthetic lipopeptide MALP-2 as adjuvant. Eur J Immunol 2003; 33(6): 1548-56.
[http://dx.doi.org/10.1002/eji.200323954] [PMID: 12778472]
[51]
Hosseini Rouzbahani N, Bayanolhagh S, Gholami M, et al. Enhanced immune responses against HIV-1 with adenovector (Gag and Tat) prime/protein boost regimen and GM-CSF injection. Iran J Allergy Asthma Immunol 2016; 15(5): 403-12.
[PMID: 27917627]
[52]
Caputo A, Gavioli R, Altavilla G, et al. Immunization with low doses of HIV-1 tat DNA delivered by novel cationic block copolymers induces CTL responses against Tat. Vaccine 2003; 21(11-12): 1103-11.
[http://dx.doi.org/10.1016/S0264-410X(02)00555-8] [PMID: 12559787]
[53]
Ramakrishna L, Anand KK, Mohankumar KM, Ranga U. Codon optimization of the tat antigen of human immunodeficiency virus type 1 generates strong immune responses in mice following genetic immunization. J Virol 2004; 78(17): 9174-89.
[http://dx.doi.org/10.1128/JVI.78.17.9174-9189.2004] [PMID: 15308713]
[54]
Borsutzky S, Ebensen T, Link C, et al. Efficient systemic and mucosal responses against the HIV-1 Tat protein by prime/boost vaccination using the lipopeptide MALP-2 as adjuvant. Vaccine 2006; 24(12): 2049-56.
[http://dx.doi.org/10.1016/j.vaccine.2005.11.025] [PMID: 16406225]
[55]
Castaldello A, Brocca-Cofano E, Voltan R, et al. DNA prime and protein boost immunization with innovative polymeric cationic core-shell nanoparticles elicits broad immune responses and strongly enhance cellular responses of HIV-1 tat DNA vaccination. Vaccine 2006; 24(29-30): 5655-69.
[http://dx.doi.org/10.1016/j.vaccine.2006.05.058] [PMID: 16781023]
[56]
Alipour S, Mahdavi A. Boosting Tat DNA vaccine with Tat protein stimulates strong cellular and humoral immune responses in mice. Biotechnol Lett 2020; 42(4): 505-17.
[http://dx.doi.org/10.1007/s10529-020-02801-8] [PMID: 31974645]
[57]
Ensoli B, Fiorelli V, Ensoli F, et al. The therapeutic phase I trial of the recombinant native HIV-1 Tat protein. AIDS 2008; 22(16): 2207-9.
[http://dx.doi.org/10.1097/QAD.0b013e32831392d4] [PMID: 18832884]
[58]
Sgadari C, Monini P, Tripiciano A, et al. Continued decay of HIV proviral DNA upon vaccination with HIV-1 Tat of subjects on long-term ART: an 8-year follow-up study. Front Immunol 2019; 10: 233.
[http://dx.doi.org/10.3389/fimmu.2019.00233] [PMID: 30815001]
[59]
Daly LM, Johnson PA, Donnelly G, Nicolson C, Robertson J, Mills KH. Innate IL-10 promotes the induction of Th2 responses with plasmid DNA expressing HIV gp120. Vaccine 2005; 23(7): 963-74.
[http://dx.doi.org/10.1016/j.vaccine.2004.03.072] [PMID: 15603899]
[60]
Qin H, Nehete PN, He H, et al. Prime-boost vaccination using chemokine-fused gp120 DNA and HIV envelope peptides activates both immediate and long-term memory cellular responses in rhesus macaques. J Biomed Biotechnol 2010; 2010: 860160.
[http://dx.doi.org/10.1155/2010/860160] [PMID: 20454526]
[61]
Abdel-Motal UM, Wang S, Awad A, Lu S, Wigglesworth K, Galili U. Increased immunogenicity of HIV-1 p24 and gp120 following immunization with gp120/p24 fusion protein vaccine expressing α-gal epitopes. Vaccine 2010; 28(7): 1758-65.
[http://dx.doi.org/10.1016/j.vaccine.2009.12.015] [PMID: 20034607]
[62]
Barnett SW, Rajasekar S, Legg H, et al. Vaccination with HIV-1 gp120 DNA induces immune responses that are boosted by a recombinant gp120 protein subunit. Vaccine 1997; 15(8): 869-73.
[http://dx.doi.org/10.1016/S0264-410X(96)00264-2] [PMID: 9234536]
[63]
Nimal S, McCormick AL, Thomas MS, Heath AW. An interferon gamma-gp120 fusion delivered as a DNA vaccine induces enhanced priming. Vaccine 2005; 23(30): 3984-90.
[http://dx.doi.org/10.1016/j.vaccine.2005.01.160] [PMID: 15917120]
[64]
Nimal S, Heath AW, Thomas MS. Enhancement of immune responses to an HIV gp120 DNA vaccine by fusion to TNF α cDNA. Vaccine 2006; 24(16): 3298-308.
[http://dx.doi.org/10.1016/j.vaccine.2006.01.020] [PMID: 16464521]
[65]
Shimada M, Yoshizaki S, Jounai N, et al. DNA vaccine expressing HIV-1 gp120/immunoglobulin fusion protein enhances cellular immunity. Vaccine 2010; 28(31): 4920-7.
[http://dx.doi.org/10.1016/j.vaccine.2010.05.035] [PMID: 20566393]
[66]
Ataman-Önal Y, Munier S, Ganée A, et al. Surfactant-free anionic PLA nanoparticles coated with HIV-1 p24 protein induced enhanced cellular and humoral immune responses in various animal models. J Control Release 2006; 112(2): 175-85.
[http://dx.doi.org/10.1016/j.jconrel.2006.02.006] [PMID: 16563545]
[67]
Gong X, Gai W, Xu J, Zhou W, Tien P. Glycoprotein 96-mediated presentation of human immunodeficiency virus type 1 (HIV-1)-specific human leukocyte antigen class I-restricted peptide and humoral immune responses to HIV-1 p24. Clin Vaccine Immunol 2009; 16(11): 1595-600.
[http://dx.doi.org/10.1128/CVI.00160-09] [PMID: 19776200]
[68]
Krupka M, Zachova K, Cahlikova R, et al. Endotoxin-minimized HIV-1 p24 fused to murine hsp70 activates dendritic cells, facilitates endocytosis and p24-specific Th1 response in mice. Immunol Lett 2015; 166(1): 36-44.
[http://dx.doi.org/10.1016/j.imlet.2015.05.010] [PMID: 26021827]
[69]
Steers NJ, Peachman KK, McClain S, Alving CR, Rao M. Liposome-encapsulated HIV-1 Gag p24 containing lipid A induces effector CD4+ T-cells, memory CD8+ T-cells, and pro-inflammatory cytokines. Vaccine 2009; 27(49): 6939-49.
[http://dx.doi.org/10.1016/j.vaccine.2009.08.105] [PMID: 19748578]
[70]
Guo S. 2016.
[71]
Pujals S, Sabidó E, Tarragó T, Giralt E. all-D proline-rich cell-penetrating peptides: a preliminary in vivo internalization study. Biochem Soc Trans 2007; 35(Pt 4): 794-6.
[http://dx.doi.org/10.1042/BST0350794] [PMID: 17635150]
[72]
Saleh T, Bolhassani A, Shojaosadati SA, Aghasadeghi MR. MPG-based nanoparticle: An efficient delivery system for enhancing the potency of DNA vaccine expressing HPV16E7. Vaccine 2015; 33(28): 3164-70. b
[http://dx.doi.org/10.1016/j.vaccine.2015.05.015] [PMID: 26001433]
[73]
Karpenko LI, Nekrasova NA, Ilyichev AA, et al. Comparative analysis using a mouse model of the immunogenicity of artificial VLP and attenuated Salmonella strain carrying a DNA-vaccine encoding HIV-1 polyepitope CTL-immunogen. Vaccine 2004; 22(13-14): 1692-9.
[http://dx.doi.org/10.1016/j.vaccine.2003.09.050] [PMID: 15068852]
[74]
Ponnappan N, Budagavi DP, Chugh A. CyLoP-1: Membrane-active peptide with cell-penetrating and antimicrobial properties. Biochim Biophys Acta Biomembr 2017; 1859(2): 167-76.
[http://dx.doi.org/10.1016/j.bbamem.2016.11.002] [PMID: 27836642]
[75]
Ponnappan N, Chugh A. Cell-penetrating and cargo-delivery ability of a spider toxin-derived peptide in mammalian cells. Eur J Pharm Biopharm 2017; 114: 145-53.
[http://dx.doi.org/10.1016/j.ejpb.2017.01.012] [PMID: 28159722]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 3
Year: 2021
Published on: 25 November, 2020
Page: [225 - 237]
Pages: 13
DOI: 10.2174/1570162X18999201125212131
Price: $65

Article Metrics

PDF: 141
HTML: 1