V2 hotspot optimized MVA vaccine expressing stabilized HIV-1 Clade C envelope Gp140 delays acquisition of heterologous Clade C Tier 2 challenges in Mamu-A*01 negative Rhesus Macaques Article Swipe
Tiffany M. Styles
,
Sailaja Gangadhara
,
Pradeep B. J. Reddy
,
Anusmita Sahoo
,
Ayalensh Shiferaw
,
Sarah Welbourn
,
Pamela A. Kozlowski
,
Cynthia A. Derdeyn
,
Vijayakumar Velu
,
Rama Rao Amara
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2022.914969
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2022.914969
Stabilized HIV envelope (Env) trimeric protein immunogens have been shown to induce strong autologous neutralizing antibody response. However, there is limited data on the immunogenicity and efficacy of stabilized Env expressed by a viral vector-based immunogen. Here, we compared the immunogenicity and efficacy of two modified vaccinia Ankara (MVA) vaccines based on variable loop 2 hotspot (V2 HS) optimized C.1086 envelope (Env) sequences, one expressing the membrane anchored gp150 (MVA-150) and the other expressing soluble uncleaved pre-fusion optimized (UFO) gp140 trimer (MVA-UFO) in a DNA prime/MVA boost approach against heterologous tier 2 SHIV1157ipd3N4 intrarectal challenges in rhesus macaques (RMs). Both MVA vaccines also expressed SIVmac239 Gag and form virus-like particles. The DNA vaccine expressed SIVmac239 Gag, C.1086 gp160 Env and rhesus CD40L as a built-in adjuvant. Additionally, all immunizations were administered intradermally (ID) to reduce induction of vaccine-specific IFNγ+ CD4 T cell responses. Our results showed that both MVA-150 and MVA-UFO vaccines induce comparable Env specific IgG responses in serum and rectal secretions. The vaccine-induced serum antibody showed ADCC and ADCVI activities against the challenge virus. Comparison with a previous study that used similar immunogens via intramuscular route (IM) showed that ID immunizations induced markedly lower SHIV specific CD4 and CD8 T cell responses compared to IM immunizations. Following challenge, MVA-UFO vaccinated animals showed a significant delay in acquisition of SHIV1157ipd3N4 infection but only in Mamu-A*01 negative macaques with an estimated vaccine efficacy of 64% per exposure. The MVA-150 group also showed a trend (p=0.1) for delay in acquisition of SHIV infection with an estimated vaccine efficacy of 57%. The vaccine-induced IFNγ secreting CD8 T cell responses showed a direct association and CD4 T cells showed an inverse association with delay in acquisition of SHIV infection. These results demonstrated that both MVA-150 and MVA-UFO immunogens induce comparable humoral and cellular immunity and the latter provides marginally better protection against heterologous tier 2 SHIV infection. They also demonstrate that DNA/MVA vaccinations delivered by ID route induce better antibody and lower CD4 and CD8 T cell responses compared to IM.
Related Topics
Concepts
Virology
Immunogenicity
Vaccinia
Modified vaccinia Ankara
Immunogen
Heterologous
Biology
HIV vaccine
Adjuvant
Neutralizing antibody
Avidity
Antibody
AIDS Vaccines
Vaccination
Virus
Immunology
Recombinant DNA
Vaccine trial
Gene
Genetics
Monoclonal antibody
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2022.914969
- https://www.frontiersin.org/articles/10.3389/fimmu.2022.914969/pdf
- OA Status
- gold
- Cited By
- 6
- References
- 57
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4286462366
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4286462366Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3389/fimmu.2022.914969Digital Object Identifier
- Title
-
V2 hotspot optimized MVA vaccine expressing stabilized HIV-1 Clade C envelope Gp140 delays acquisition of heterologous Clade C Tier 2 challenges in Mamu-A*01 negative Rhesus MacaquesWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-07-22Full publication date if available
- Authors
-
Tiffany M. Styles, Sailaja Gangadhara, Pradeep B. J. Reddy, Anusmita Sahoo, Ayalensh Shiferaw, Sarah Welbourn, Pamela A. Kozlowski, Cynthia A. Derdeyn, Vijayakumar Velu, Rama Rao AmaraList of authors in order
- Landing page
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https://doi.org/10.3389/fimmu.2022.914969Publisher landing page
- PDF URL
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https://www.frontiersin.org/articles/10.3389/fimmu.2022.914969/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.frontiersin.org/articles/10.3389/fimmu.2022.914969/pdfDirect OA link when available
- Concepts
-
Virology, Immunogenicity, Vaccinia, Modified vaccinia Ankara, Immunogen, Heterologous, Biology, HIV vaccine, Adjuvant, Neutralizing antibody, Avidity, Antibody, AIDS Vaccines, Vaccination, Virus, Immunology, Recombinant DNA, Vaccine trial, Gene, Genetics, Monoclonal antibodyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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6Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 2, 2023: 1, 2022: 1Per-year citation counts (last 5 years)
- References (count)
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57Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.that | 146, 181, 190, 289, 317 |
| abstract_inverted_index.tier | 90, 310 |
| abstract_inverted_index.used | 182 |
| abstract_inverted_index.were | 129 |
| abstract_inverted_index.with | 177, 228, 252, 279 |
| abstract_inverted_index.(Env) | 3, 61 |
| abstract_inverted_index.(MVA) | 48 |
| abstract_inverted_index.(UFO) | 78 |
| abstract_inverted_index.ADCVI | 170 |
| abstract_inverted_index.CD40L | 121 |
| abstract_inverted_index.Here, | 36 |
| abstract_inverted_index.IFNγ | 261 |
| abstract_inverted_index.These | 286 |
| abstract_inverted_index.based | 50 |
| abstract_inverted_index.boost | 86 |
| abstract_inverted_index.cells | 274 |
| abstract_inverted_index.delay | 216, 246, 280 |
| abstract_inverted_index.gp140 | 79 |
| abstract_inverted_index.gp150 | 68 |
| abstract_inverted_index.gp160 | 117 |
| abstract_inverted_index.group | 239 |
| abstract_inverted_index.lower | 195, 328 |
| abstract_inverted_index.other | 72 |
| abstract_inverted_index.route | 187, 323 |
| abstract_inverted_index.serum | 159, 165 |
| abstract_inverted_index.shown | 9 |
| abstract_inverted_index.study | 180 |
| abstract_inverted_index.there | 18 |
| abstract_inverted_index.trend | 243 |
| abstract_inverted_index.viral | 33 |
| abstract_inverted_index.(RMs). | 98 |
| abstract_inverted_index.Ankara | 47 |
| abstract_inverted_index.C.1086 | 59, 116 |
| abstract_inverted_index.IFNγ+ | 138 |
| abstract_inverted_index.better | 306, 325 |
| abstract_inverted_index.direct | 269 |
| abstract_inverted_index.induce | 11, 152, 295, 324 |
| abstract_inverted_index.latter | 303 |
| abstract_inverted_index.rectal | 161 |
| abstract_inverted_index.reduce | 134 |
| abstract_inverted_index.rhesus | 96, 120 |
| abstract_inverted_index.showed | 145, 167, 189, 213, 241, 267, 275 |
| abstract_inverted_index.strong | 12 |
| abstract_inverted_index.trimer | 80 |
| abstract_inverted_index.virus. | 175 |
| abstract_inverted_index.(p=0.1) | 244 |
| abstract_inverted_index.DNA/MVA | 318 |
| abstract_inverted_index.MVA-150 | 148, 238, 291 |
| abstract_inverted_index.MVA-UFO | 150, 210, 293 |
| abstract_inverted_index.against | 88, 172, 308 |
| abstract_inverted_index.animals | 212 |
| abstract_inverted_index.hotspot | 55 |
| abstract_inverted_index.humoral | 297 |
| abstract_inverted_index.induced | 193 |
| abstract_inverted_index.inverse | 277 |
| abstract_inverted_index.limited | 20 |
| abstract_inverted_index.protein | 5 |
| abstract_inverted_index.results | 144, 287 |
| abstract_inverted_index.similar | 183 |
| abstract_inverted_index.soluble | 74 |
| abstract_inverted_index.vaccine | 112, 231, 255 |
| abstract_inverted_index.However, | 17 |
| abstract_inverted_index.anchored | 67 |
| abstract_inverted_index.antibody | 15, 166, 326 |
| abstract_inverted_index.approach | 87 |
| abstract_inverted_index.built-in | 124 |
| abstract_inverted_index.cellular | 299 |
| abstract_inverted_index.compared | 38, 204, 335 |
| abstract_inverted_index.efficacy | 26, 42, 232, 256 |
| abstract_inverted_index.envelope | 2, 60 |
| abstract_inverted_index.immunity | 300 |
| abstract_inverted_index.macaques | 97, 227 |
| abstract_inverted_index.markedly | 194 |
| abstract_inverted_index.membrane | 66 |
| abstract_inverted_index.modified | 45 |
| abstract_inverted_index.negative | 226 |
| abstract_inverted_index.previous | 179 |
| abstract_inverted_index.provides | 304 |
| abstract_inverted_index.specific | 155, 197 |
| abstract_inverted_index.trimeric | 4 |
| abstract_inverted_index.vaccines | 49, 101, 151 |
| abstract_inverted_index.vaccinia | 46 |
| abstract_inverted_index.variable | 52 |
| abstract_inverted_index.(MVA-150) | 69 |
| abstract_inverted_index.(MVA-UFO) | 81 |
| abstract_inverted_index.Following | 208 |
| abstract_inverted_index.Mamu-A*01 | 225 |
| abstract_inverted_index.SIVmac239 | 104, 114 |
| abstract_inverted_index.adjuvant. | 125 |
| abstract_inverted_index.challenge | 174 |
| abstract_inverted_index.delivered | 320 |
| abstract_inverted_index.estimated | 230, 254 |
| abstract_inverted_index.exposure. | 236 |
| abstract_inverted_index.expressed | 30, 103, 113 |
| abstract_inverted_index.induction | 135 |
| abstract_inverted_index.infection | 221, 251 |
| abstract_inverted_index.optimized | 58, 77 |
| abstract_inverted_index.prime/MVA | 85 |
| abstract_inverted_index.response. | 16 |
| abstract_inverted_index.responses | 157, 203, 266, 334 |
| abstract_inverted_index.secreting | 262 |
| abstract_inverted_index.uncleaved | 75 |
| abstract_inverted_index.Comparison | 176 |
| abstract_inverted_index.Stabilized | 0 |
| abstract_inverted_index.activities | 171 |
| abstract_inverted_index.autologous | 13 |
| abstract_inverted_index.challenge, | 209 |
| abstract_inverted_index.challenges | 94 |
| abstract_inverted_index.comparable | 153, 296 |
| abstract_inverted_index.expressing | 64, 73 |
| abstract_inverted_index.immunogen. | 35 |
| abstract_inverted_index.immunogens | 6, 184, 294 |
| abstract_inverted_index.infection. | 285, 313 |
| abstract_inverted_index.marginally | 305 |
| abstract_inverted_index.particles. | 109 |
| abstract_inverted_index.pre-fusion | 76 |
| abstract_inverted_index.protection | 307 |
| abstract_inverted_index.responses. | 142 |
| abstract_inverted_index.sequences, | 62 |
| abstract_inverted_index.stabilized | 28 |
| abstract_inverted_index.vaccinated | 211 |
| abstract_inverted_index.virus-like | 108 |
| abstract_inverted_index.acquisition | 218, 248, 282 |
| abstract_inverted_index.association | 270, 278 |
| abstract_inverted_index.demonstrate | 316 |
| abstract_inverted_index.intrarectal | 93 |
| abstract_inverted_index.secretions. | 162 |
| abstract_inverted_index.significant | 215 |
| abstract_inverted_index.administered | 130 |
| abstract_inverted_index.demonstrated | 288 |
| abstract_inverted_index.heterologous | 89, 309 |
| abstract_inverted_index.neutralizing | 14 |
| abstract_inverted_index.vaccinations | 319 |
| abstract_inverted_index.vector-based | 34 |
| abstract_inverted_index.Additionally, | 126 |
| abstract_inverted_index.immunizations | 128, 192 |
| abstract_inverted_index.intradermally | 131 |
| abstract_inverted_index.intramuscular | 186 |
| abstract_inverted_index.SHIV1157ipd3N4 | 92, 220 |
| abstract_inverted_index.immunizations. | 207 |
| abstract_inverted_index.immunogenicity | 24, 40 |
| abstract_inverted_index.vaccine-induced | 164, 260 |
| abstract_inverted_index.vaccine-specific | 137 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 89 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 10 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8399999737739563 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.64638434 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |