Palabras clave
partículas semejantes a bacterias
presentación de antígenos
adyuvantes
respuesta inmune adaptativa
Cómo citar
Resumen
Introducción: El desarrollo de una vacuna contra el virus del herpes simple tipo 2 (HSV-2), el cual causa una infección de transmisión sexual de por vida, sería un gran paso para mejorar la salud sexual y reproductiva mundial. Objetivos: Estudiar las respuestas inmunes de mucosa y sistémica inducidas por una vacuna experimental, consistente en partículas semejantes a bacterias (BLP) derivadas de lactobacilos, que conservan su matriz de peptidoglicano y exponen el antígeno gD del HSV-2 en su superficie gracias a la fusión con dominios LysM. Materiales y métodos: Ratones BALB/c de seis semanas de edad fueron inmunizados por vía nasal con el complejo His-Acglu-gD-BLP027 los días 0, 14 y 28. Como control, se administró His-Acglu-gD por via intranasal o His-gD con adyuvante completo de Freund por vía peritoneal. Se evaluaron los niveles de inmunoglobulinas específicas en suero y en lavado broncoalveolar (BAL), así como la producción de citoquinas por parte de los esplenocitos, en respuesta a la reestimulación antigénica. Resultados: La vacuna experimental indujo mayores niveles de IgA en BAL en comparación con los ratones inmunizados con el adyuvante de Freund. Conclusiones: Este nuevo sistema de presentación de antígenos podría ser una herramienta útil para el desarrollo de vacunas mucosas que estimulen la inmunidad local y a distancia.
Citas
Kardani K, Basimi P, Fekri M, Bolhassani A. Antiviral therapy for the sexually transmitted viruses: recent updates on vaccine development. Expert Rev Clin Pharmacol. 2020;13(9):1001-46
https://doi.org/10.1080/17512433.2020.1814743
Johnston C, Gottlieb SL, Wald A. Status of vaccine research and development of vaccines for herpes simplex virus. Vaccine. 2016;34(26):2948-52
https://doi.org/10.1016/j.vaccine.2015.12.076
Spicknall IH, Looker KJ, Gottlieb SL, Chesson HW, Schiffer JT, Elmes J, et al. Review of mathematical models of HSV-2 vaccination: Implications for vaccine development. Vaccine. 2019;37(50):7396-407
https://doi.org/10.1016/j.vaccine.2018.02.067
Stinn T, Kuntz S, Varon D, Huang ML, Selke S, Njikan S, et al. Subclinical Genital Herpes Shedding in HIV/Herpes Simplex Virus 2-Coinfected Women during Antiretroviral Therapy Is Associated with an Increase in HIV Tissue Reservoirs and Potentially Promotes HIV Evolution. J Virol. 2020;95(1)
https://doi.org/10.1128/JVI.01606-20
LaTourette PC, 2nd, Awasthi S, Desmond A, Pardi N, Cohen GH, Weissman D, et al. Protection against herpes simplex virus type 2 infection in a neonatal murine model using a trivalent nucleoside-modified mRNA in lipid nanoparticle vaccine. Vaccine. 2020;38(47):7409-13
https://doi.org/10.1016/j.vaccine.2020.09.079
Byrne CM, Gantt S, Coombs D. Effects of spatiotemporal HSV-2 lesión dynamics and antiviral treatment on the risk of HIV-1 acquisition. PLoS Comput Biol. 2018;14(4):e1006129
https://doi.org/10.1371/journal.pcbi.1006129
Egan KP, Hook LM, Naughton A, Pardi N, Awasthi S, Cohen GH, et al. An HSV-2 nucleoside-modified mRNA genital herpes vaccine containing glycoproteins gC, gD, and gE protects mice against HSV-1 genital lesions and latent infection. PLoS Pathog. 2020;16(7):e1008795
https://doi.org/10.1371/journal.ppat.1008795
Bi J, Li F, Zhang M, Wang H, Lu J, Zhang Y, et al. An HIV-1 vaccine based on bacterium-like particles elicits Env-specific mucosal immune responses. Immunol Lett. 2020;222:29-39
https://doi.org/10.1016/j.imlet.2020.03.002
Sato A, Suwanto A, Okabe M, Sato S, Nochi T, Imai T, et al. Vaginal memory T cells induced by intranasal vaccination are critical for protective T cell recruitment and prevention of genital HSV-2 disease. J Virol. 2014;88(23):13699-708
https://doi.org/10.1128/JVI.02279-14
Lycke N. Recent progress in mucosal vaccine development: potential and limitations. Nat Rev Immunol. 2012;12(8):592-605
https://doi.org/10.1038/nri3251
Villena J, Chiba E, Tomosada Y, Salva S, Marranzino G, Kitazawa H, et al. Orally administered Lactobacillus rhamnosus modulates the respiratory immune response triggered by the viral pathogen-associated molecular pattern poly(I:C). BMC Immunol. 2012;13:53
https://doi.org/10.1186/1471-2172-13-53
Villena J, Medina M, Vintini E, Alvarez S. Stimulation of respiratory immunity by oral administration of Lactococcus lactis. Can J Microbiol. 2008;54(8):630-8
https://doi.org/10.1139/W08-052
Villena J, Racedo S, Aguero G, Bru E, Medina M, Alvarez S. Lactobacillus casei improves resistance to pneumococcal respiratory infection in malnourished mice. J Nutr. 2005;135(6):1462-9
https://doi.org/10.1093/jn/135.6.1462
Tonetti FR, Islam MA, Vizoso-Pinto MG, Takahashi H, Kitazawa H, Villena J. Nasal priming with immunobiotic lactobacilli improves the adaptive immune response against influenza virus. Int Immunopharmacol. 2020;78:106115
https://doi.org/10.1016/j.intimp.2019.106115
Villena J, Barbieri N, Salva S, Herrera M, Alvarez S. Enhanced immune response to pneumococcal infection in malnourished mice nasally treated with heat-killed Lactobacillus casei. Microbiol Immunol. 2009;53(11):636-46
https://doi.org/10.1111/j.1348-0421.2009.00171.x
Raya Tonetti F, Arce L, Salva S, Alvarez S, Takahashi H, Kitazawa H, et al. Immunomodulatory Properties of Bacterium-Like Particles Obtained From Immunobiotic Lactobacilli: Prospects for Their Use as Mucosal Adjuvants. Front Immunol. 2020;11:1
https://doi.org/10.3389/fimmu.2020.00015
Visweswaran GR, Leenhouts K, van Roosmalen M, Kok J, Buist G. Exploitingthe peptidoglycan-binding motif, LysM, for medical and industrial applications. Appl Microbiol Biotechnol. 2014;98(10):4331-45
https://doi.org/10.1007/s00253-014-5633-7
van Roosmalen ML, Kanninga R, El Khattabi M, Neef J, Audouy S, Bosma T, et al. Mucosal vaccine delivery of antigens tightly bound to an adjuvant particle made from food-grade bacteria. Methods. 2006;38(2):144-9
https://doi.org/10.1016/j.ymeth.2005.09.015
Bosma T, Kanninga R, Neef J, Audouy SA, van Roosmalen ML, Steen A, et al. Novel surface display system for proteins on non-genetically modified gram-positive bacteria. Appl Environ Microbiol. 2006;72(1):880-9
https://doi.org/10.1128/AEM.72.1.880-889.2006
Van Braeckel-Budimir N, Haijema BJ, Leenhouts K. Bacterium-like particles for efficient immune stimulation of existing vaccines and new subunit vaccines in mucosal applications. Front Immunol. 2013;4:282
https://doi.org/10.3389/fimmu.2013.00282
Raya-Tonetti F, Muller M, Sacur J, Kitazawa H, Villena J, Vizoso-Pinto MG. Novel LysM motifs for antigen display on lactobacilli for mucosal immunization. Sci Rep. 2021;11(1):21691
https://doi.org/10.1038/s41598-021-01087-8
Osterman A, Vizoso Pinto MG, Haase R, Nitschko H, Jager S, Sander M, et al. Systematic screening for novel, serologically reactive Hepatitis E Virus epitopes. Virology journal. 2012;9:28
https://doi.org/10.1186/1743-422X-9-28
Vizoso Pinto MG, Pfrepper KI, Janke T, Noelting C, Sander M, Lueking A, et al. A systematic approach for the identification of novel, serologically reactive recombinant Varicella-Zoster Virus (VZV) antigens. Virology journal. 2010;7:165
https://doi.org/10.1186/1743-422X-7-165
Domingo C, Gadea I, Pardeiro M, Castilla C, Fernandez S, Fernandez- Clua MA, et al. Immunological properties of a DNA plasmid encoding a chimeric protein of herpes simplex virus type 2 glycoprotein B and glycoproteinD. Vaccine. 2003;21(25-26):3565-74
https://doi.org/10.1016/S0264-410X(03)00423-7
Arce LP, Raya Tonetti MF, Raimondo MP, Muller MF, Salva S, Alvarez S, et al. Oral Vaccination with Hepatitis E Virus Capsid Protein and Immunobiotic Bacterium-Like Particles Induce Intestinal and Systemic Immunity in Mice. Probiotics and antimicrobial proteins. 2019
https://doi.org/10.1007/s12602-019-09598-7
LeCureux JS, Dean GA. Lactobacillus Mucosal Vaccine Vectors: Immune Responses against Bacterial and Viral Antigens. mSphere. 2018;3(3)
https://doi.org/10.1128/mSphere.00061-18
Konstantinov SR, Smidt H, de Vos WM, Bruijns SC, Singh SK, Valence F, et al. S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proc Natl Acad Sci U S A. 2008;105(49):19474-9
https://doi.org/10.1073/pnas.0810305105
Song J, Lang F, Zhao N, Guo Y, Zhang H. Vaginal Lactobacilli Induce Differentiation f Monocytic Precursors Toward Langerhans-like Cells: inVitro Evidence. Frontiers in immunology. 2018;9:2437 eCollection 2018.
https://doi.org/10.3389/fimmu.2018.02437
Chentoufi AA, Dhanushkodi NR, Srivastava R, Prakash S, Coulon PA, Zayou L, et al. Combinatorial Herpes Simplex Vaccine Strategies: From Bedside to Bench and Back. Front Immunol. 2022;13:849515 eCollection 2022.
https://doi.org/10.3389/fimmu.2022.849515
Bernstein DI, Flechtner JB, McNeil LK, Heineman T, Oliphant T, Tasker S, et al. Therapeutic HSV-2 vaccine decreases recurrent virus shedding and recurrent genital herpes disease. Vaccine. 2019;37(26):3443-50
https://doi.org/10.1016/j.vaccine.2019.05.009
Schiffer JT, Swan DA, Corey L, Wald A. Rapid viral expansion and short drug half-life explain the incomplete effectiveness of current herpes simplex virus 2-directed antiviral agents. Antimicrob Agents Chemother. 2013;57(12):5820-9
https://doi.org/10.1128/AAC.01114-13
Kardani K, Basimi P, Fekri M, Bolhassani A. Antiviral therapy for the sexually transmitted viruses: recent updates on vaccine development. Expert Rev Clin Pharmacol. 2020:1-46
https://doi.org/10.1080/17512433.2020.1814743
Krishnan R, Stuart PM. Developments in Vaccination for Herpes Simplex Virus. Front Microbiol. 2021;12:798927
https://doi.org/10.3389/fmicb.2021.798927
ames C, Harfouche M, Welton NJ, Turner KM, Abu-Raddad LJ, Gottlieb SL, et al. Herpes simplex virus: global infection prevalence and incidence estimates, 2016. Bull World Health Organ. 2020;98(5):315-29
https://doi.org/10.2471/BLT.19.237149
Zhang I, Hsiao Z, Liu F. Development of Genome Editing Approaches against Herpes Simplex Virus Infections. Viruses. 2021;13(2).
https://doi.org/10.3390/v13020338
Du R, Wang L, Xu H, Wang Z, Zhang T, Wang M, et al. A novel glycoprotein D-specific monoclonal antibody neutralizes herpes simplex virus. Antiviral Res. 2017;147:131-41.
https://doi.org/10.1016/j.antiviral.2017.10.013
Burn Aschner C, Pierce C, Knipe DM, Herold BC. Vaccination Route as a Determinant of Protective Antibody Responses against Herpes Simplex Virus. Vaccines (Basel). 2020;8(2)
https://doi.org/10.3390/vaccines8020277
Stanberry LR, Spruance SL, Cunningham AL, Bernstein DI, Mindel A, Sacks S, et al. Glycoprotein-D-adjuvant vaccine to prevent genital herpes. N Engl J Med. 2002;347(21):1652-61
https://doi.org/10.1056/NEJMoa011915
Belshe RB, Leone PA, Bernstein DI, Wald A, Levin MJ, Stapleton JT, et al. Efficacy results of a trial of a herpes simplex vaccine. N Engl J Med. 2012;366(1):34-43
https://doi.org/10.1056/NEJMoa1103151
Dropulic LK, Oestreich MC, Pietz HL, Laing KJ, Hunsberger S, LumbardK, et al. A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection. J Infect Dis. 2019;220(6):990-1000
https://doi.org/10.1093/infdis/jiz225
Bernard MC, Barban V, Pradezynski F, de Montfort A, Ryall R, Caillet C, et al. Immunogenicity, protective efficacy, and non-replicative status of the HSV-2 vaccine candidate HSV529 in mice and guinea pigs. PLoS One. 2015;10(4):e0121518
https://doi.org/10.1371/journal.pone.0121518
Mestecky J, Moldoveanu Z, Russell MW. Immunologic uniqueness of the genital tract: challenge for vaccine development. Am J Reprod Immunol. 2005;53(5):208-14