A long-term stable cold-chain-friendly HIV mRNA vaccine encoding multi-epitope viral protease cleavage site immunogens inducing immunogen-specific protective T cell immunity
The lack of success in clinical trials for HIV vaccines highlights the need to explore novel strategies for vaccine development. Research on highly exposed seronegative (HESN) HIV-resistant Kenyan female sex workers revealed naturally protective immunity is correlated with a focused immune response...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2024.2377606 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850169931837997056 |
|---|---|
| author | Subhra Mandal Jayadri Sekhar Ghosh Saroj Chandra Lohani Miaoyun Zhao Yilun Cheng Rachel Burrack Ma Luo Qingsheng Li |
| author_facet | Subhra Mandal Jayadri Sekhar Ghosh Saroj Chandra Lohani Miaoyun Zhao Yilun Cheng Rachel Burrack Ma Luo Qingsheng Li |
| author_sort | Subhra Mandal |
| collection | DOAJ |
| description | The lack of success in clinical trials for HIV vaccines highlights the need to explore novel strategies for vaccine development. Research on highly exposed seronegative (HESN) HIV-resistant Kenyan female sex workers revealed naturally protective immunity is correlated with a focused immune response mediated by virus-specific CD8 T cells. Further studies indicated that the immune response is unconventionally focused on highly conserved sequences around HIV viral protease cleavage sites (VPCS). Thus, taking an unconventional approach to HIV vaccine development, we designed lipid nanoparticles loaded with mRNA that encodes multi-epitopes of VPCS (MEVPCS-mRNA LNP), a strategic design to boost antigen presentation by dendritic cells, promoting effective cellular immunity. Furthermore, we developed a novel cold-chain compatible mRNA LNP formulation, ensuring long-term stability and compatibility with cold-chain storage/transport, widening accessibility of mRNA LNP vaccine in low-income countries. The in-vivo mouse study demonstrated that the vaccinated group generated VPCS-specific CD8 memory T cells, both systemically and at mucosal sites of viral entry. The MEVPCS-mRNA LNP vaccine-induced CD8 T cell immunity closely resembled that of the HESN group and displayed a polyfunctional profile. Notably, it induced minimal to no activation of CD4 T cells. This proof-of-concept study underscores the potential of the MEVPCS-mRNA LNP vaccine in eliciting CD8 T cell memory specific to the highly conserved multiple VPCS, consequently having a broad coverage in human populations and limiting viral escape mutation. The MEVPCS-mRNA LNP vaccine holds promise as a candidate for an effective prophylactic HIV vaccine. |
| format | Article |
| id | doaj-art-e8ea14064b7948269b8453f1458e408a |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-e8ea14064b7948269b8453f1458e408a2025-08-20T02:20:37ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512024-12-0113110.1080/22221751.2024.2377606A long-term stable cold-chain-friendly HIV mRNA vaccine encoding multi-epitope viral protease cleavage site immunogens inducing immunogen-specific protective T cell immunitySubhra Mandal0Jayadri Sekhar Ghosh1Saroj Chandra Lohani2Miaoyun Zhao3Yilun Cheng4Rachel Burrack5Ma Luo6Qingsheng Li7Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USANebraska Center for Virology, Department of Plant Pathology, University of Nebraska-Lincoln, Lincoln, NE, USANebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USANebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USANebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USANebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USADepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, CanadaNebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USAThe lack of success in clinical trials for HIV vaccines highlights the need to explore novel strategies for vaccine development. Research on highly exposed seronegative (HESN) HIV-resistant Kenyan female sex workers revealed naturally protective immunity is correlated with a focused immune response mediated by virus-specific CD8 T cells. Further studies indicated that the immune response is unconventionally focused on highly conserved sequences around HIV viral protease cleavage sites (VPCS). Thus, taking an unconventional approach to HIV vaccine development, we designed lipid nanoparticles loaded with mRNA that encodes multi-epitopes of VPCS (MEVPCS-mRNA LNP), a strategic design to boost antigen presentation by dendritic cells, promoting effective cellular immunity. Furthermore, we developed a novel cold-chain compatible mRNA LNP formulation, ensuring long-term stability and compatibility with cold-chain storage/transport, widening accessibility of mRNA LNP vaccine in low-income countries. The in-vivo mouse study demonstrated that the vaccinated group generated VPCS-specific CD8 memory T cells, both systemically and at mucosal sites of viral entry. The MEVPCS-mRNA LNP vaccine-induced CD8 T cell immunity closely resembled that of the HESN group and displayed a polyfunctional profile. Notably, it induced minimal to no activation of CD4 T cells. This proof-of-concept study underscores the potential of the MEVPCS-mRNA LNP vaccine in eliciting CD8 T cell memory specific to the highly conserved multiple VPCS, consequently having a broad coverage in human populations and limiting viral escape mutation. The MEVPCS-mRNA LNP vaccine holds promise as a candidate for an effective prophylactic HIV vaccine.https://www.tandfonline.com/doi/10.1080/22221751.2024.2377606HIV vaccineprophylaxiscold-chain friendly mRNA LNPsprotective immunitymulti-epitope viral PCS |
| spellingShingle | Subhra Mandal Jayadri Sekhar Ghosh Saroj Chandra Lohani Miaoyun Zhao Yilun Cheng Rachel Burrack Ma Luo Qingsheng Li A long-term stable cold-chain-friendly HIV mRNA vaccine encoding multi-epitope viral protease cleavage site immunogens inducing immunogen-specific protective T cell immunity Emerging Microbes and Infections HIV vaccine prophylaxis cold-chain friendly mRNA LNPs protective immunity multi-epitope viral PCS |
| title | A long-term stable cold-chain-friendly HIV mRNA vaccine encoding multi-epitope viral protease cleavage site immunogens inducing immunogen-specific protective T cell immunity |
| title_full | A long-term stable cold-chain-friendly HIV mRNA vaccine encoding multi-epitope viral protease cleavage site immunogens inducing immunogen-specific protective T cell immunity |
| title_fullStr | A long-term stable cold-chain-friendly HIV mRNA vaccine encoding multi-epitope viral protease cleavage site immunogens inducing immunogen-specific protective T cell immunity |
| title_full_unstemmed | A long-term stable cold-chain-friendly HIV mRNA vaccine encoding multi-epitope viral protease cleavage site immunogens inducing immunogen-specific protective T cell immunity |
| title_short | A long-term stable cold-chain-friendly HIV mRNA vaccine encoding multi-epitope viral protease cleavage site immunogens inducing immunogen-specific protective T cell immunity |
| title_sort | long term stable cold chain friendly hiv mrna vaccine encoding multi epitope viral protease cleavage site immunogens inducing immunogen specific protective t cell immunity |
| topic | HIV vaccine prophylaxis cold-chain friendly mRNA LNPs protective immunity multi-epitope viral PCS |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2024.2377606 |
| work_keys_str_mv | AT subhramandal alongtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT jayadrisekharghosh alongtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT sarojchandralohani alongtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT miaoyunzhao alongtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT yiluncheng alongtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT rachelburrack alongtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT maluo alongtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT qingshengli alongtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT subhramandal longtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT jayadrisekharghosh longtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT sarojchandralohani longtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT miaoyunzhao longtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT yiluncheng longtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT rachelburrack longtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT maluo longtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity AT qingshengli longtermstablecoldchainfriendlyhivmrnavaccineencodingmultiepitopeviralproteasecleavagesiteimmunogensinducingimmunogenspecificprotectivetcellimmunity |