2016
DOI: 10.1128/jvi.00812-16
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Relationship between Vaccine-Induced Antibody Capture of Infectious Virus and Infection Outcomes following Repeated Low-Dose Rectal Challenges with Simian Immunodeficiency Virus SIVmac251

Abstract: Antibodies are known to enhance in vitro infection by human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). We measured the ability of antibodies induced by ALVAC-SIV/gp120 vaccination, given with alum or MF59 adjuvant, to capture infectious SIVmac251 and determined the association between capture and infection outcomes following lowdose, repeated rectal challenge of rhesus macaques. We found that capture correlated with the number of transmitted/founder (T/F) variants that established in… Show more

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Cited by 7 publications
(5 citation statements)
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“…Since monocytes and macrophages can be infected with HIV-1, one theory is that antibody-mediated phagocytosis may have caused increased viral infection of these phagocytes. More specifically, enhancement may have been due solely to weakly or non-neutralizing antibodies that remain capable of engaging but not neutralizing HIV-1 virus (151). However, it is notable that no enhancement of infection in the vaccine arm was observed in the VAX003 and VAX004 clinical trials, both of which elicited high levels of non-neutralizing antibodies (152, 153).…”
Section: Potential For Adcp To Enhance Viral Infectionmentioning
confidence: 99%
“…Since monocytes and macrophages can be infected with HIV-1, one theory is that antibody-mediated phagocytosis may have caused increased viral infection of these phagocytes. More specifically, enhancement may have been due solely to weakly or non-neutralizing antibodies that remain capable of engaging but not neutralizing HIV-1 virus (151). However, it is notable that no enhancement of infection in the vaccine arm was observed in the VAX003 and VAX004 clinical trials, both of which elicited high levels of non-neutralizing antibodies (152, 153).…”
Section: Potential For Adcp To Enhance Viral Infectionmentioning
confidence: 99%
“…The partial protection by F240 is intriguing and complicates interpreting results of the study. One possibility based on in vitro analysis, was the greater ability of F240 compared to b6 and b12 to capture infectious virions although recently this characteristic has not held up as advantageous [57]. The mechanisms behind F240 protection are unknown, but it was hypothesized that even though functionally inactive, the gp41 “stump” epitope recognized by F240 on otherwise infectious virions provided a footing for Fc receptor mediated mechanisms that decreased infectivity of the virus inoculum.…”
Section: Progress In Developing Primate Models and Lessons From Passimentioning
confidence: 99%
“…V2 specific antibodies appeared important but there were other important signals of protection, including induction of Env-dependent intestinal lymphoid cells. However, antibodies from MF59-adjuvanted ALVAC/gp120 vaccinated NHPs captured more infectious virus than the alum group, resulting in a higher number of T/F strains [57]. Thus understanding the relative importance of neutralizing and capture antibodies in mucosal acquisition models remains a key goal of adjuvant and antigen design for HIV vaccines.…”
Section: Developing Vaccines That Overcome Env Diversity By Inducing mentioning
confidence: 99%
“…Nonetheless, the reported differences between alum and MF59 adjuvants in whether they aid protective responses do not readily conform with some other findings. For example, MF59 induces stronger virion-capturing antibody responses than alum ( 110 ), but virion capture has been linked to both protective and infection-enhancing net effects ( 37 , 66 , 110 112 ) ( Table 2 ), and alum is less effective than MF59 in supporting the induction of serum antibody responses to Env immunogens, including the anti-V2 IgG response, a reported CoP candidate ( 15 , 16 ).…”
Section: The Influence Of Cop Analyses On Vaccine Designmentioning
confidence: 99%