Abstract | BACKGROUND:
Antiviral antibodies, especially those with neutralizing activity against the incoming strain, are potentially important immunological effectors to control human immunodeficiency virus ( HIV) infection. While neutralizing activity appears to be central in sterile protection against HIV infection, the entity of inhibitory mechanisms via HIV and simian immunodeficiency virus (SIV)-specific antibodies remains elusive. The recent HIV vaccine trial RV144 and studies in nonhuman primate models have indicated controversial protective efficacy of HIV/SIV-specific non-neutralizing binding antibodies (non-NAbs). While reports on HIV-specific non-NAbs have demonstrated virus inhibitory activity in vitro, whether non-NAbs could also alter the pathogenic course of established SIV replication in vivo, likewise via neutralizing antibody (NAb) administration, has been unclear. Here, we performed post- infection passive immunization of SIV-infected rhesus macaques with polyclonal SIV-specific, antibody-dependent cell-mediated viral inhibition (ADCVI)-competent non-NAbs. METHODS AND FINDINGS: Ten lots of polyclonal immunoglobulin G ( IgG) were prepared from plasma of ten chronically SIVmac239-infected, NAb-negative rhesus macaques, respectively. Their binding capacity to whole SIVmac239 virions showed a propensity similar to ADCVI activity. A cocktail of three non-NAb lots showing high virion-binding capacity and ADCVI activity was administered to rhesus macaques at day 7 post-SIVmac239 challenge. This resulted in an infection course comparable with control animals, with no significant difference in set point plasma viral loads or immune parameters. CONCLUSIONS: Despite virus-specific suppressive activity of the non-NAbs having been observed in vitro, their passive immunization post- infection did not result in SIV control in vivo. Virion binding and ADCVI activity with lack of virus neutralizing activity were indicated to be insufficient for antibody-triggered non-sterile SIV control. More diverse effector functions or sophisticated localization may be required for non-NAbs to impact HIV/SIV replication in vivo.
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Authors | Taku Nakane, Takushi Nomura, Shoi Shi, Midori Nakamura, Taeko K Naruse, Akinori Kimura, Tetsuro Matano, Hiroyuki Yamamoto |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 9
Pg. e73453
( 2013)
ISSN: 1932-6203 [Electronic] United States |
PMID | 24039947
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Neutralizing
- Antibodies, Viral
- SAIDS Vaccines
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Topics |
- Animals
- Antibodies, Neutralizing
- Antibodies, Viral
(immunology, therapeutic use)
- Humans
- Immunization, Passive
- Macaca mulatta
(immunology, virology)
- SAIDS Vaccines
(immunology, therapeutic use)
- Simian Acquired Immunodeficiency Syndrome
(immunology, prevention & control, virology)
- Simian Immunodeficiency Virus
(immunology)
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