Anti-HIV IgM protects against mucosal SHIV transmission

Abstract

Our primate model data provide the first proof-of-concept that mucosal IgM can prevent mucosal HIV transmission and have implications for HIV prevention and vaccine development.

Mucosal Antibodies: Defending Epithelial Barriers against HIV-1 Invasion

“…Thirty minutes later, the animals were challenged with a single, high-dose of simian-human immunodeficiency virus (SHIV). The first proof-of-concept that IgM can protect against mucosal SHIV challenge was given by our group [10]. Likewise, we also gave the first evidence that dIgA nmAbs can prevent SHIV transmission [6].…”

“…We performed our studies in RMs that were exposed to R5-tropic SHIV strains carrying an HIV-1 clade C envelope known to be recently transmitted [32,33]. The data are summarized in Figure 1B [3][4][5][6][7][8][9][10]. In the first study [6], we performed passive mucosal immunization and tested a panel of recombinant human mAbs engineered to have the same epitope specificity conferred by the VH and VL genes in the context of human dIgA1, dIgA2, and IgG1 backbones ( Figure 1B, middle and bottom sections).…”

“…When considering the presence of different Ig classes in mucosal fluids, we came to realize that no information existed for the potential of anti-HIV-1 IgM to block mucosal virus transmission. Therefore, we generated 33C6-IgM [10] and tested it with its IgG1 counterpart in the same RM/SHIV mucosal challenge model system ( Figure 1B, top section). The recombinant form of 33C6-IgM was generated from mAb 33C6-IgG1 [35], which also recognizes the same conserved V3 loop crown in HIV-1 Env as HGN194.…”

“…However, Abs can greatly impact virus acquisition at mucosal levels. A number of groups have performed passive immunizations in nonhuman primates using mucosal application of nmAbs and shown protection against simianhuman immunodeficiency virus (SHIV) challenge [3][4][5][6][7][8][9][10]; reviewed in [11] (summarized in Figure 1B). Generation and transport of mucosal Igs in a normal host.…”

“…Thus, retaining infectious HIV-1 particles at mucosal linings is the first major defense mechanism that prevents the virions from getting close to their target cells. Using passive immunization as an investigational tool that can clearly delineate cause and effect, we have shown that anti-HIV-1 dimeric IgA (dIgA), IgG [6], and-most recently-also pentameric IgM [10] are effective defenders at the mucosal level.…”