Will infants need to be vaccinated, or can maternal vaccination suffice? Or will the selective pressure of the vaccinated response potentially select a more virulent form that may cross into the child? Can passive immunization switch the fitness of the viral subtype that passes on to babies? == Table 2. transmission. Actually in source poor settings, the infrastructure for neonatal vaccination is already in place. Although rare, both passive and active vaccination tests have been successfully completed in pediatric populations. Unfortunately, little success in influencing MTCT has been shown. Mainly, a correlate of safety in any type of transmission, including MTCT, is definitely unknown. Data helps a role for antibodies in effecting strain and transmission during MTCT. The role of antibodies in MTCT is usually reviewed with a focus on recent passive immunization and considerations for future studies. Keywords:Immunotherapy, antibodies, vaccine, immunoglobulin, neutralizing, pediatric, HIV, maternal-to-child transmission == Preventing Mother to Child Transmission of HIV == Maternal-to-child-transmission (MTCT) remains the major cause of global pediatric HIV contamination [1]. Every day almost 2000 children succumb to contamination [2], the majority of which L-cysteine is through maternal to child transmission. Since peripartum antiretrovirals were shown to successfully decrease MTCT, initially shown by ACTG Protocol 076 [3], there has been continued success with improved implimentation of this strategy [4,5]. Currently, the majority of intervention trials directly targeted at MTCT relate to either pharmacologic or behavioral interventions. However, there are significant advantages for global vaccine development to studying vaccinations in the setting of MTCT [6,7]. Although vaccine implementation in resource constrained settings has its own challenges, recent encouraging results increases the plausibility that immune therapies will play a major role in preventing MTCT [8]. The results of past and current immunization and immunotherapy trials and their feasibility in protecting against breast-milk transmission will be reviewed herein. == Lack of Focus on MTCT in Previous Adult Trials == Despite the recent success of the RV-144 Thai trial, little is known of protecting MTCT by vaccination. No active immunization strategy phase III trial addressing this question has been completed [9]. In fact, there have only been three large-scale vaccine studies to date with primary outcome measures being protection from contamination in adult populations. Unfortunately, even for their primary outcome measure, the results have been generally disappointing. In the VAX 003/004 trials, using a recombinant gp120 protein, a total of 2546 IV drug-users were enrolled. No L-cysteine protection was seen using this construct. Regarding MTCT, which was not a planned evaluation, females comprised only 6.6% of the total enrollees with only 10 total women becoming infected between the groups [10]. There is no current plan to follow up potential pregnancies in these L-cysteine individuals and regardless, it will be difficult to draw conclusions from such a small number of L-cysteine individuals. In fact, a review of women enrolled in various HIV phase I and II vaccine trials showed that this pregnancy rate was only 2.9% [11,12]. Unfortunately, the STEP Trial, which used an adenovirus (rAd5)-based vaccine, showed enhanced acquisition of HIV-1 in individuals who had received the vaccine. This effect appeared to correlate with preexisting immunity to the Ad5 vector. Both preexisting non-neutralizing antibodies against Ad5 and preexisting mucosal immunity have been proposed as explanations for this result [13,14]. Of the 3000 study participants enrolled in the Step trial, 90 participants included in both arms became infected and received at least 1 dose of vaccine or placebo during the study. It is difficult to remark on MTCT as only 2 of these participants that became infected were female. Overall, on long-term follow-up of those infected in both arms, no differences in viral load or T cell functional indices were seen [15] so it is unlikely that this type of regimen would be effective in preventing MTCT. == Encouraging Results of the RV-144 L-cysteine Trial == More recently, the controversial RV-144 trial with a canarypox virus (vCP) primary (ALVAC) and a recombinant gp120 AIDSVAX (clade B and E) boost was performed [16]. This trial had roughly 8000 enrollees per arm with roughly 1/3 being female. This trial showed modest efficacy of 31% reduction in risk. This has been a rather controversial obtaining. Statistically, this efficacy was only significant in one of three forms of statistical analysis. An independent analysis estimated the ability of this vaccine to have a true protective effect as 71% [17]. Although the AIDSVAX gp120 has not Rabbit Polyclonal to MC5R been shown to raise broadly neutralizing antibodies, a combined analysis of the phase I and II ALVAC-HIV and gp120 AIDSVAX primeboost studies showed a similar rate of HIV-1 contamination to the RV-144 trial: 0.59 per 100 person-years in the vaccine group and 1.2 per 100 person-years in the placebo group. This group analysis equaled a vaccine efficacy of 50% and had no effect on viral load [18]. This paralleled the results of the larger RV144 study. Interestingly, the RV144 proposed protective effect was most prominent in the lowest risk.