The pathogenicity of a strain of simian herpesvirus SA8 in one month old conventional and gnotobiotic baboons was investigated. Intratracheal inoculation resulted in a mortality rate of 1/5 in the conventional and 1/4 in the gnotobiotic group. Disease became apparent after 3 days and was characterized by respiratory distress, reduced formula intake, weight loss and fever in both groups. Isolation of herpesvirus from the respiratory tract, lymphoid organs, kidneys, adrenals, and CNS was more frequent by explant culturing than by routine procedures. Although there was a significant difference in total white blood counts (WBC), with higher values in conventional vs. gnotobiotic infants, the absolute number of lymphocytes was not different. The lower number of WBCs apparently was due to fewer polymorphonuclear leukocytes in the gnotobiotic baboons. Infection resulted in a leukopenia 5 days post infection (p.i.) and a leukocytosis 10 days p.i. in both groups. The animals, which succumbed, had acute necrotizing fibrinous pneumonia. Intranuclear inclusion bodies typical for herpesviruses were present. All the surviving infant baboons had subacute interstitial pneumonia, when sacrificed 35 days p.i.

BACKGROUND: Although it is rare, blood-transmitted HIV infection can occur when a donor presents in the window period between HIV-1 exposure and the first appearance of detectable p24 antigen.STUDY DESIGN AND METHODS: To study this seronegative window period, a chimpanzee (X034) was inoculated with 38 median tissue culture infective doses of HIV-1 IIIB; serum and peripheral blood mononuclear cells were obtained one to two times per week for 12 weeks and then biweekly for 12 weeks. Infectivity was monitored by the detection of serum HIV RNA, cell-associated HIV DNA, p24 antigen, and anti-HIV and by coculture methods.RESULTS: No HIV markers were noted until 5 weeks after inoculation, at which time virus was isolated and HIV RNA and DNA were detected in plasma and cells, respectively. Anti-HIV and HIV p24 antigen were not present until 8 weeks after inoculation. Plasma and cells obtained from Chimpanzee X034 3 or 4 weeks after exposure were then sequentially inoculated into a second chimpanzee (X176); no HIV infection was observed in this animal during serial follow-up for 24 weeks after each inoculation. In contrast, when the fifth-week HIV-1 RNA- and DNA-positive sample was inoculated, Chimpanzee X176 was unequivocally infected with HIV-1.CONCLUSIONS: Nucleic acid testing narrowed the seronegative window by 3 weeks (37%). More important, there was no demonstrable infectivity in either plasma or peripheral blood mononuclear cells obtained before molecular markers were detectable. This suggests that the infectious window may be considerably shorter than the total window as measured from exposure and that nucleic acid testing might not only shorten the seronegative window, but totally prevent transfusion-transmitted HIV infection.

We would like to comment on the controversy concerning the use of a virulent strain of human immunodeficiency virus (HIV) to assess the protective efficacy of candidate HIV vaccines (A. M. Prince and L. Andrus, Letters, Science 's Compass, 18 Dec. p. [2195][1]; N. L. Letvin, ibid. ). We believe that this must be viewed from both scientific and ethical perspectives. The controversy stems from the report of a chimpanzee that developed an AIDS-like syndrome 10 years after infection with various laboratory isolates of HIV and which was euthanized in 1996 ([1][2]). Inoculation of 40 milliliters of blood from this chimpanzee to a second animal resulted in an extremely high acute viremia (>107 HIV RNA molecules per milliliter of plasma) and a rapid depletion of CD4+ cells within 14 weeks after infection. The virulence of the primary infection in this animal is not representative of most primary infections in humans. Acute viremia in humans is characteristically 10- to 100-fold lower, and CD4+ cell depletion does not occur until several years after infection. Use of a challenge virus having unusual virulence could seriously jeopardize the HIV vaccine effort, because protection against such viruses could be missed with vaccines that effectively protect against less virulent wild-type HIV. Suitable challenge viruses for vaccine evaluation should have virulence characteristics similar to those of wild-type viruses that infect humans. They should also ideally be primary isolates grown only on peripheral blood lymphocytes because of the relative resistance of such viruses to antibody-mediated neutralization. An expanded stock of the HIV-1Han2 isolate was recently developed by Program EVA (European Vaccine Against AIDS) to fulfill these requirements ([2][3]). This clade-B primary isolate exhibits growth characteristics in chimpanzees similar to those seen in humans. It reliably infects chimpanzees using small challenge inocula (10 to 100-tissue-culture infectious doses) and maintains a detectable chronic viremia similar to that obtained with the laboratory isolate HIV-1Lai. It does not cause AIDS rapidly, if at all. From an ethical perspective, our concerns about the use of virulent HIV strains stem to a large extent from precedents set in the field of simian immunodeficiency virus (SIV)/SHIV (a genetically engineered hybrid virus with an HIV envelope and an SIV core) research in monkeys. Pathogenic SIV strains have emerged that have subsequently been passaged through monkeys to develop isolates with increased virulence for that species and which cause death within weeks after infection. We point out that euthanasia of chimpanzees (our nearest relative) is universally condemned. The development of virulent HIV strains that cause AIDS in a short time would necessitate euthanasia and should be opposed on that ground alone. We urge those who carry out vaccine research in the chimpanzee model to seriously question the use of virulent HIV challenge inocula from both a scientific and an ethical standpoint. 1. [↵][4]1. F. J. Novembre 2. et al. , J. Virol 71, 4086 (1997). [OpenUrl][5][Abstract/FREE Full Text][6] 2. [↵][7]1. W. J. Bogers 2. et al. , J. Gen. Virol. 79, 2895 (1998). [OpenUrl][8][Abstract/FREE Full Text][9] [1]: /lookup/doi/10.1126/science.282.5397.2194d [2]: #ref-1 [3]: #ref-2 [4]: #xref-ref-1-1 View reference 1 in text [5]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2BVirology%26rft.stitle%253DJ.%2BVirol.%26rft.aulast%253DNovembre%26rft.auinit1%253DF.%2BJ.%26rft.volume%253D71%26rft.issue%253D5%26rft.spage%253D4086%26rft.epage%253D4091%26rft.atitle%253DDevelopment%2Bof%2BAIDS%2Bin%2Ba%2Bchimpanzee%2Binfected%2Bwith%2Bhuman%2Bimmunodeficiency%2Bvirus%2Btype%2B1%26rft_id%253Dinfo%253Apmid%252F9094687%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [6]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoianZpIjtzOjU6InJlc2lkIjtzOjk6IjcxLzUvNDA4NiI7czo0OiJhdG9tIjtzOjI1OiIvc2NpLzI4My81NDA1LzExMTUuNS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30= [7]: #xref-ref-2-1 View reference 2 in text [8]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2BGeneral%2BVirology%26rft.stitle%253DJ.%2BGen.%2BVirol.%26rft.aulast%253DBogers%26rft.auinit1%253DW.%2BM.%26rft.volume%253D79%26rft.issue%253D12%26rft.spage%253D2895%26rft.epage%253D2903%26rft.atitle%253DCharacteristics%2Bof%2Bprimary%2Binfection%2Bof%2Ba%2BEuropean%2Bhuman%2Bimmunodeficiency%2Bvirus%2Btype%2B1%2Bclade%2BB%2Bisolate%2Bin%2Bchimpanzees%26rft_id%253Dinfo%253Apmid%252F9880002%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [9]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoidmlyIjtzOjU6InJlc2lkIjtzOjEwOiI3OS8xMi8yODk1IjtzOjQ6ImF0b20iO3M6MjU6Ii9zY2kvMjgzLzU0MDUvMTExNS41LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==

Abstract: Immune responses mediated by CD8+ lymphocytes have been correlated with protection from HIV infection and disease progression in humans and nonhuman primates. The CD8+ cell population is heterogeneous in terms of biological function and phenotype. We have undertaken a review of the current state of knowledge of subtypes of CD8+ cells and their role in immune responses directed to HIV and related primate lentiviruses. Differences in the pathogenesis of lentivirus infections in various primate hosts were examined and the possible roles of the various subpopulations of CD8+ lymphocytes in the resistance and/or susceptibility to lentivirus‐related disease were compared.

A combination AIDS vaccine approach consisting of priming with adenovirus-HIV-1MNgp160 recom-binants followed by boosting with HIV-1SF2 gp120 was evaluated in chimpanzees. Long-lasting protection, requiring only three immunizations, was achieved against a low-dose challenge with the SF2 strain of HIV-1 and a subsequent high-dose SF2 challenge administered 1 year later without an intervening boost. Notably, neutralizing antibody responses against both clinical and laboratory isolates developed in three chimpanzees and persisted until the time of high-dose challenge. The possibility that cytotoxic T-lymphocytes contribute to low-dose protection of a chimpanzee lacking neutralizing antibodies is suggested. Our results validate the live vector priming/subunit booster approach and should stimulate interest in assessing this combination vaccine approach in humans.

Chimpanzees infected with human immunodeficiency virus type 1 (HIV-1) are used to model acquired immunodeficiency syndrome (AIDS). Since the central nervous system (CNS) is involved in AIDS, we performed an immunovirological study in 18 chimpanzees inoculated up to 87 months prior to the study (mean, 45 months) with HIV-1 and 8 uninfected controls. Serum and cerebrospinal fluid (CSF) IgG and albumin levels of infected chimpanzees never exceeded those of controls. The CSF/serum albumin ratio was elevated in 1 of 18 infected chimpanzees compared to controls; however, all animals had an elevated ratio indicating a more open blood-brain barrier relative to humans. The intrathecal IgG production index was elevated in only 1 of 18 infected chimpanzees compared to controls. Identical serum and CSF IgG bands were found by isoelectric focusing in 2 of 8 controls and in 1 of 18 infected chimpanzees. None of these bands reacted with recombinant HIV-1 p24gag or gp 120env. HIV-1 was isolated from the peripheral blood of 4 of 18 infected chimpanzees but never from the paired CSF samples. Anti-HIV-1 antibody was detected by a enzyme-linked immunosorbent assay in 18 of 18 paired serum and CSF samples and by Western blot in 18 of 18 serum and 13 of 18 CSF samples from infected chimpanzees without a difference in pattern. Polymerase chain reaction analysis on brain tissue of one animal was negative for HIV-1 sequences. Our results demonstrate that, unlike human infection, chimpanzees inoculated with HIV-1 show no evidence of isolatable virus in the CSF and no evidence of intrathecal anti-HIV-1 antibody synthesis up to several years after experimental infection. The lack of CNS involvement may contribute to the delay or suppression of clinical disease in infected chimpanzees.

The present article represents a consensus view of the appropriate utilization of chimpanzees in AIDS research arrived at as a result of a meeting of a group of scientists involved in AIDS research with chimpanzees and bioethicists. The paper considers which types of studies are scientifically justifiable in this species, the conditions under which such studies should be carried out, and the conditions which should be encouraged for post-experimental retirement of these animals.

Recombinant adenovirus (Ad)-human immunodeficiency virus (HIV) vaccines expressing HIVIIIB Env and Gag proteins were evaluated for immunogenicity in chimpanzees following intranasal administration. When Ad7-, Ad4-, and Ad5-vectored vaccines were administered sequentially at 0, 24, and 52 weeks, respectively, to three chimpanzees, the inoculations resulted in limited virus replication in the nasopharynx, but extensive Ad-HIV replication occurred in the intestine. High-titered IgG serum antibody responses to Env and Gag that were nonneutralizing were induced following booster administration of Ad4-HIV recombinant viruses. Following the Ad5-HIV booster, low levels of neutralizing antibodies as well as V3 loop antibodies were induced in all three chimpanzees that persisted for several months. Administration of a gp160 subunit vaccine (baculovirus derived) in SAF-m 24 weeks later boosted broadly neutralizing serum antibodies that peaked within 1 month of the injection. Two additional subunit boosters 19 and 37 weeks later were progressively less effective at stimulating serum neutralizing antibody responses. Substantial local immune responses were induced in nasal, vaginal, and salivary secretions following the third Ad-HIV intranasal immunization. These responses were further boosted with the gp160 subunit vaccine, which also stimulated production of rectal antibodies. The predominant responses in all secretions tested were of the IgG isotype, although some IgA responses were also detected. Strong blastogenic responses to HIV recombinant Envand Gag proteins were induced after each immunization.

Coexpression of biologically active interleukin 6 (IL-6), an immunoregulator, and hepatitis B virus surface antigen (HBsAg), an immunogen, was obtained using an adenovirus type 7 (Ad7) vector. Two recombinant adenoviruses (re-Ad) containing both the HBsAg and IL6 genes were constructed: one virus was capable of expressing IL6 with its signal peptide (spIL6) (Ad7::spIL6::HBsAg), and the second virus lacked this sequence (Ad7::IL6::HBsAg). A third recombinant contained only HBsAg (Ad7::HBsAg). All three Ad constructs were plaque purified and characterized in the A549 human lung cell line. The growth kinetics of the recombinants were similar to wild-type (wt) Ad7. The production and secretion of HBsAg (p24 and gp27) from cells infected with each re-Ad were at a level greater than 9 micrograms/10(6) cells by 118 h postinfection. Two IL-6 of approx. 24 and 27 kDa were produced and secreted into the culture medium from cells infected with Ad7::spIL6::HBsAg, and maximal accumulation occurred by 92 h p.i. at a level > 260 ng/10(6) cells. One cell-associated IL-6 of approx. 23 kDa was produced from cells infected with Ad7::IL6::HBsAg at a level > 12 ng/10(6) cells. Importantly, the Ad-produced IL-6 were determined to be biologically active by enhancing immunoglobulin production in lymphoblastoid cells. The co-production of IL-6 with HBsAg did not affect growth of these recombinant Ad, immunoreactivity of HBsAg, or the biological activity of IL-6 in tissue culture cells.

Haemagglutinin (HA), the major surface glycoprotein of influenza virus, is a potent immunogen against which viral neutralizing antibodies are directed. Studies of the three-dimensional structure of HA have identified major antigenic sites on the molecule. We have exploited HA as a carrier for small antigenic regions (epitopes) of the HIV-1 envelope (env) glycoprotein. Using recombinant DNA techniques, the epitopes were inserted in-frame into a known antigenic site of HA to produce HA-epitope chimeras. Guinea-pigs and mice immunized with these chimeras in combination with adjuvant generated significant immune responses against the carrier HA and also produced epitope-specific antibodies that recognized the native whole HIV-1 env. One of the chimeras which contained a V3-loop sequence of HIV-1 env elicited neutralizing antibodies against the homologous strain of HIV-1. The antibodies against HA and the inserted epitopes remained at high levels for up to 72 weeks. Remarkably, these responses were generated with low doses of immunogens containing only nanogram quantities of the inserted epitopes. These results suggest the utility of HA as a carrier to allow selective antibody induction against foreign epitopes, and offer a new approach for vaccine development as well as for the production of monospecific antibodies useful in diagnostics and research.

Recombinant human adenovirus (Ad) type 4-, 5-, and 7-vectored vaccines expressing either the HIV env or gag-protease genes were tested for immunogenicity in three chimpanzees. The first phase of the vaccination protocol consisted of a primary and two booster immunizations with Ad-HIVs by the oral route of administration, followed by a single booster immunization with Gag and/or Env subunit vaccines. The second phase of the vaccination protocol consisted of intranasal administration of Ad-HIVs previously administered by the oral route. Following the first phase adenovirus was shed into stools for only 1-7 days and modest type-specific anti-adenovirus neutralizing antibody titers were induced. Strong anti-Env binding antibody responses were detected in all three animals following the second oral booster immunization. One chimpanzee responded with a low-titered type-specific neutralizing antibody response to HIV. Cell-mediated immune responses to Env were not detected after the primary vaccination, but were detected following all booster immunizations. Administration of the Gag subunit vaccine boosted both humoral and cell-mediated immune responses to Gag antigens. In contrast, the Env subunit vaccine boosted cellular but not humoral immune responses. In the second phase of the vaccination protocol, both virus shedding and anti-adenovirus responses were enhanced. All three chimpanzees responded to the intranasal administration of Ad7-HIVs with boosted anti-HIV serum responses, including low-titered type-specific neutralizing antibodies, elicited anti-HIV antibodies at secretory sites, and stimulated cell-mediated immune responses to both Gag and Env antigens.

The performance of captive chimpanzees (Pan troglodytes) during a simulated foraging activity was compared to that reported for the foraging behavior of wild chimpanzees. The ability to find hidden fruit in a large outdoor play area was measured for 34 subjects housed in ten separate groups. Sex differences were apparent, with females searching for and finding significantly more fruit than males did. Chimpanzees of high and medium dominance rank found more fruit than those of low rank. Neither age nor stage of the female sexual cycle exerted an influence. The subjects became more proficient at finding fruit during the second block of trials. The results reflect possible influences of captivity on chimpanzee social behavior.

Chimpanzees used for biomedical research must be bred in captivity because of restrictions on importation. Because they are large and expensive animals, population sizes at breeding facilities are limited. This implies that inbreeding at some level is inevitable and that genetic management techniques should be employed to minimize matings between related individuals. The purpose of this paper is to consider the genetic history of the chimpanzee colony at the Southwest Foundation for Biomedical Research (SFBR) and to suggest ways in which genetic variability may be affected by management schemes. A total of 339 chimpanzees resided at SFBR between January, 1980, and January, 1990. Although only one mating between related individuals has occurred so far, the average level of kinship in the colony and between potential breeders is increasing. Population structure techniques were employed to assess the mating patterns which have occurred and to explore the degree of change in the characteristics of potential mates. A "gene dropping" simulation method was used to predict expected levels of heterozygosity and strategies for maintaining variability by increasing the breeding portion of the population were evaluated using a simulation approach. © 1995 Wiley-Liss, Inc.

Three different species of nonhuman primates (baboons [Papio hamadryas], rhesus monkeys [Macaca mulatta], and African green monkeys [Cercopithecus aethiops]) were evaluated for their natural killer cell activity, and for the ability of their peripheral blood mononuclear cells to proliferate in response to known mitogens (concanavalin A, phytohemagglutinin, and pokeweed mitogen) and to react with a panel of mouse monoclonal antibodies directed against human leukocyte surface antigens. Rhesus monkeys displayed the highest natural killer cell cytotoxic activity (185.7 +/- 33 lytic units) compared with those of baboons (83.8 +/- 19 lytic units) and of African green monkeys from West Africa (39.08 +/- 8 lytic units) and from the Caribbean basin (37.9 +/- 9 lytic units). No correlation was observed between the natural killer cell cytotoxic activity and the percentage of CD16+ natural killer cells among the three species studied. High spontaneous proliferative capacity was observed in African green monkeys obtained from West Africa compared with those of the other species studied. Although no significant differences were noted in T and B cell mitogen-induced in vitro proliferation, baboon mononuclear cells were less responsive to concanavalin A (stimulation index of 16 +/- 3 [mean +/- standard error of mean]) than to phytohemagglutinin (stimulation index of 47 +/- 12). However, rhesus and African green monkey cells proliferated more efficiently in response to concanavalin A. Unlike in human beings where the ratio between helper-inducer (CD4+) and cytotoxic-suppressor (CD8+) T-lymphocytes is generally greater than 1, the CD4+/CD8+ ratios in baboons and rhesus and African green monkeys were 0.58, 0.69, and 0.35, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Chimpanzees infected with human immunodeficiency virus type 1 produce antibodies against the variable regions of the external envelope glycoprotein gp120. All five variable regions contain an epitope which is recognized by at least one of five chimpanzee sera. Each of the sera recognized a different pattern of epitopes. It is suggested that this varying response contributes to the emergence of variant viruses in the host. In contrast with the variability of the chimpanzees' response to replicating virus, that of baboons to a candidate recombinant vaccine is more uniform. Baboons injected with recombinant gp120 produced high levels of antibodies to epitopes within both the variable and conserved regions which coincided with epitopes previously shown to induce neutralizing antibodies.

Recombinant human adenoviruses (Ads) that replicate in the intestinal tract offer a novel, yet practical, means of immunoprophylaxis against a wide variety of viral and bacterial pathogens. For some infectious agents such as human immunodeficiency virus (HIV), the potential for residual infectious material in vaccine preparations must be eliminated. Therefore, recombinant human Ads that express noninfectious HIV or other microbial proteins are attractive vaccine candidates. To test such an approach for HIV, we chose an experimental model of AIDS based on simian immunodeficiency virus (SIV) infection of macaques. Our data demonstrate that the SIV Env gene products are expressed in cultured cells after infection with a recombinant Ad containing both SIV env and rev genes. An E3 deletion vector derived from a mutant of human Ad serotype 5 that efficiently replicates in both human and monkey cells was used to bypass the usual host range restriction of Ad infection. In addition, we show that the SIV rev gene is properly spliced from a single SIV subgenomic DNA fragment and that the Rev protein is expressed in recombinant Ad-SIV-infected human as well as monkey cells. The expression of SIV gene products in suitable live Ad vectors provides an excellent system for studying the regulation of SIV gene expression in cultured cells and evaluating the immunogenicity and protective efficacy of SIV proteins in macaques.

CD8+ cell antiviral activity and cytomegalovirus (CMV) were investigated in vivo as possible cofactors influencing the outcome of HIV-1 infection. The role of CD8+ cell suppression of HIV replication was evaluated by depleting CD8+ cells in two infected chimpanzees by inoculation with monoclonal anti-CD8 antibodies. Two other infected animals were injected with chimpanzee CMV (CCMV)-indected human fibroblasts to determine if exposure to this virus would induce HIV replication. Treatment with anti-CD8 antibody resulted in recovery of virus from the CD4+ lymphocytes of one animal at 1, 4, and 6 months, and from a second animal at 1 month postinoculation. In contrast, virus had been recovered only once or not at all from these infected chimpanzees for 4 years prior to treatment. Similarly, HIV was recovered from the CD4+ cells of the two animals 2 to 3 months after inoculation of CCMV-infected fibroblasts but not after inoculation of control uninfected fibroblasts. These studies suggest that CD8+ cell-mediated suppression and the presence of other viruses (such as CMV) could act as cofactors in influencing the extent of HIV-1 replication in vivo and, possibly, progression to disease.

CD4, the cell-surface receptor for the human immunodeficiency virus (HIV), is a member of the immunoglobulin (Ig) gene superfamily. It contains 4 extracellular sequences homologous to Ig variable domains, the first of which (V1) is sufficient for binding to HIV. To develop CD4 as an anti-HIV therapeutic, we engineered a CD4 immunoadhesin (CD4-IgG)--a fusion protein containing the V1 and V2 domains of CD4 with the hinge and Fc regions of human Ig heavy chain. A chimeric protein of this type has several advantages compared to the soluble receptor, including a greatly extended in vivo half-life and greater avidity for HIV; moreover, like an antibody, it performs effector functions via its Fc domains, such as complement activation and antibody-dependent cell-mediated cytotoxicity. In vivo experiments show that CD4-IgG protects against HIV-I IIIB infection of chimpanzees when administered prior to viral challenge. In addition, CD4-IgG is transferred efficiently across the placenta from mother to fetus in rhesus monkeys. To evaluate its safety in humans, we conducted a phase-I clinical trial in adult patients with AIDS and AIDS-related complex. We found that, in a total of 16 patients, administration of CD4-IgG was well tolerated at doses up to 1000 micrograms/kg of body weight, with no important clinical or immunological toxicities noted. Given its unique properties, particularly the ability of CD4-IgG to cross the placenta, we plan to focus future clinical efforts on preventing infection of newborns via maternal-fetal transfer of HIV.