Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies.
Recent immune correlates analysis from the RV144 vaccine trial has renewed interest in the role of non-neutralizing antibodies in mediating protection from infection. While neutralizing antibodies have proven difficult to induce through vaccination, extra-neutralizing antibodies, such as those that...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4018276?pdf=render |
| _version_ | 1818862907573665792 |
|---|---|
| author | Anne-Sophie Dugast Ying Chan Michelle Hoffner Anna Licht Joseph Nkolola Hualin Li Hendrik Streeck Todd J Suscovich Musie Ghebremichael Margaret E Ackerman Dan H Barouch Galit Alter |
| author_facet | Anne-Sophie Dugast Ying Chan Michelle Hoffner Anna Licht Joseph Nkolola Hualin Li Hendrik Streeck Todd J Suscovich Musie Ghebremichael Margaret E Ackerman Dan H Barouch Galit Alter |
| author_sort | Anne-Sophie Dugast |
| collection | DOAJ |
| description | Recent immune correlates analysis from the RV144 vaccine trial has renewed interest in the role of non-neutralizing antibodies in mediating protection from infection. While neutralizing antibodies have proven difficult to induce through vaccination, extra-neutralizing antibodies, such as those that mediate antibody-dependent cellular cytotoxicity (ADCC), are associated with long-term control of infection. However, while several non-neutralizing monoclonal antibodies have been tested for their protective efficacy in vivo, no studies to date have tested the protective activity of naturally produced polyclonal antibodies from individuals harboring potent ADCC activity. Because ADCC-inducing antibodies are highly enriched in elite controllers (EC), we passively transferred highly functional non-neutralizing polyclonal antibodies, purified from an EC, to assess the potential impact of polyclonal non-neutralizing antibodies on a stringent SHIV-SF162P3 challenge in rhesus monkeys. Passive transfer of a low-dose of ADCC inducing antibodies did not protect from infection following SHIV-SF162P3 challenge. Passively administered antibody titers and gp120-specific, but not gp41-specific, ADCC and antibody induced phagocytosis (ADCP) were detected in the majority of the monkeys, but did not correlate with post infection viral control. Thus these data raise the possibility that gp120-specific ADCC activity alone may not be sufficient to control viremia post infection but that other specificities or Fc-effector profiles, alone or in combination, may have an impact on viral control and should be tested in future passive transfer experiments. |
| first_indexed | 2024-12-19T10:07:19Z |
| format | Article |
| id | doaj.art-a3af037709d04423b28265a7eeaede41 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T10:07:19Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a3af037709d04423b28265a7eeaede412022-12-21T20:26:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9722910.1371/journal.pone.0097229Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies.Anne-Sophie DugastYing ChanMichelle HoffnerAnna LichtJoseph NkololaHualin LiHendrik StreeckTodd J SuscovichMusie GhebremichaelMargaret E AckermanDan H BarouchGalit AlterRecent immune correlates analysis from the RV144 vaccine trial has renewed interest in the role of non-neutralizing antibodies in mediating protection from infection. While neutralizing antibodies have proven difficult to induce through vaccination, extra-neutralizing antibodies, such as those that mediate antibody-dependent cellular cytotoxicity (ADCC), are associated with long-term control of infection. However, while several non-neutralizing monoclonal antibodies have been tested for their protective efficacy in vivo, no studies to date have tested the protective activity of naturally produced polyclonal antibodies from individuals harboring potent ADCC activity. Because ADCC-inducing antibodies are highly enriched in elite controllers (EC), we passively transferred highly functional non-neutralizing polyclonal antibodies, purified from an EC, to assess the potential impact of polyclonal non-neutralizing antibodies on a stringent SHIV-SF162P3 challenge in rhesus monkeys. Passive transfer of a low-dose of ADCC inducing antibodies did not protect from infection following SHIV-SF162P3 challenge. Passively administered antibody titers and gp120-specific, but not gp41-specific, ADCC and antibody induced phagocytosis (ADCP) were detected in the majority of the monkeys, but did not correlate with post infection viral control. Thus these data raise the possibility that gp120-specific ADCC activity alone may not be sufficient to control viremia post infection but that other specificities or Fc-effector profiles, alone or in combination, may have an impact on viral control and should be tested in future passive transfer experiments.http://europepmc.org/articles/PMC4018276?pdf=render |
| spellingShingle | Anne-Sophie Dugast Ying Chan Michelle Hoffner Anna Licht Joseph Nkolola Hualin Li Hendrik Streeck Todd J Suscovich Musie Ghebremichael Margaret E Ackerman Dan H Barouch Galit Alter Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies. PLoS ONE |
| title | Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies. |
| title_full | Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies. |
| title_fullStr | Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies. |
| title_full_unstemmed | Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies. |
| title_short | Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies. |
| title_sort | lack of protection following passive transfer of polyclonal highly functional low dose non neutralizing antibodies |
| url | http://europepmc.org/articles/PMC4018276?pdf=render |
| work_keys_str_mv | AT annesophiedugast lackofprotectionfollowingpassivetransferofpolyclonalhighlyfunctionallowdosenonneutralizingantibodies AT yingchan lackofprotectionfollowingpassivetransferofpolyclonalhighlyfunctionallowdosenonneutralizingantibodies AT michellehoffner lackofprotectionfollowingpassivetransferofpolyclonalhighlyfunctionallowdosenonneutralizingantibodies AT annalicht lackofprotectionfollowingpassivetransferofpolyclonalhighlyfunctionallowdosenonneutralizingantibodies AT josephnkolola lackofprotectionfollowingpassivetransferofpolyclonalhighlyfunctionallowdosenonneutralizingantibodies AT hualinli lackofprotectionfollowingpassivetransferofpolyclonalhighlyfunctionallowdosenonneutralizingantibodies AT hendrikstreeck lackofprotectionfollowingpassivetransferofpolyclonalhighlyfunctionallowdosenonneutralizingantibodies AT toddjsuscovich lackofprotectionfollowingpassivetransferofpolyclonalhighlyfunctionallowdosenonneutralizingantibodies AT musieghebremichael lackofprotectionfollowingpassivetransferofpolyclonalhighlyfunctionallowdosenonneutralizingantibodies AT margareteackerman lackofprotectionfollowingpassivetransferofpolyclonalhighlyfunctionallowdosenonneutralizingantibodies AT danhbarouch lackofprotectionfollowingpassivetransferofpolyclonalhighlyfunctionallowdosenonneutralizingantibodies AT galitalter lackofprotectionfollowingpassivetransferofpolyclonalhighlyfunctionallowdosenonneutralizingantibodies |