We identified two anti-HIV-1 Env mAbs of mucosal origin through B cell isolation from colostrum which displayed HIV-1-neutralizing activity. These mAbs represent two of the first HIV-1 Env-specific mAbs to be isolated from a mucosal compartment, and the first to be isolated from colostrum. As most HIV-1 transmission occurs via mucosal barriers, the study of effective mucosal B cell responses is critical to the design of HIV-1 vaccine candidates that will elicit protective antibodies from mucosal B cell populations. This study represents an initial step in determining the breadth and function of HIV-1 Env-specific antibodies that are inducible in mucosal compartments.
MAb CH07 is a highly autoreactive antibody that binds to linear epitopes within the gp120 C5 region and gp41 fusion domain and displays weak neutralization against a clade AE virus. The C5 domain is a hydrophilic region within gp120 that roughly 80% of HIV-1-infected individuals make antibodies against 
. In contrast, the fusion domain is a hydrophobic region of gp41 that is essential for viral fusion 
. Remarkably, no anti-HIV-1 Env mAbs reported to date are specific for this region. It may not be surprising, however, that this antibody was isolated from a woman who was recently pregnant. The cellular immune system of a pregnant woman is suppressed in order to prevent immune-mediated rejection of the fetus. The precise mechanisms of this suppression are poorly understood, however, in the combined state of pregnancy and HIV-1 infection, autoreactive B cells may be subject to less stringent tolerance control and may not be deleted as efficiently. This setting may make the appearance of polyreactive anti-HIV-1 antibodies more likely, but it is unknown if such antibodies are common among HIV-1-infected pregnant women. Due to the weak neutralization and strong autoreactivity of mAb CH07, CH07-like mucosal antibody responses are not likely a suitable vaccine target in the general population. However, it is also possible that the use of HIV-1 vaccine candidates in both infected and uninfected pregnant women may result in an altered, and possibly more robust, HIV-1-neutralizing antibody responses compared to nonpregnant individuals, but at this time such surmises remain speculative.
The identified colostrum mAb CH08 is a CD4i mAb with moderate-breadth HIV-1-neutralizing activity, representing a potential target for transmission-blocking mucosal responses. CH08 shares many traits with the subclass of CD4i antibodies including 1–69 VH
gene usage, long acidic CDR loop, and a sulfated tyrosine within the CDR region 
. However, neutralization studies show that CH08 has slightly broader and more potent neutralization capacity than other CD4i mAbs, indicating a potentially more accessible gp120 binding site. Structural characterization of the CH08 binding site may be important for guiding efforts to elicit these types of antibodies in uninfected individuals. Importantly, CH08 was not polyreactive, and thus vaccine induction of CH08-like mucosal antibodies may be feasible.
Recent nonhuman primate and human studies of HIV-1-specific immune responses in breast milk have indicated that virus-specific IgG primarily mediates the neutralizing and non-neutralizing responses in milk, despite the total antibody pool in milk being mainly comprised of IgA 
. It is therefore not surprising that these HIV-1 Env-specific colostrum mAbs, CH07 and CH08, are IgG isotype, and this is consistent with previous work demonstrating that IgG-secreting B cells in milk predominate over IgA-secreting B cells 
. Further characterization of locally-produced anti-HIV-1 functional IgG responses in milk may illuminate why the majority of nursing infants of HIV-1-infected infants are protected against HIV-1 acquisition, despite chronic, daily mucosal HIV-1 exposure. In fact, mucosal IgG responses, rather than mucosal IgA responses, may be a more appropriate target of maternal vaccines aimed at interrupting postnatal HIV transmission.