Human responses against HER-2-positive cancer cells in human immune system-engrafted mice.

BACKGROUND: Human immune system (HIS)-engrafted mice are new tools to investigate human immune responses. Here, we used HIS mice to study human immune responses against human HER-2-positive cancer cells and their ability to control tumour growth and metastasis. METHODS: BALB/c Rag2(-/-), Il2rg(-/-) mice were engrafted with CD34(+) or CD133(+) human cord blood hematopoietic stem cells (HSC) and vaccinated with human HER-2-positive cancer cells SK-OV-3 combined to human IL-12. RESULTS: Both CD34(+) or CD133(+) human HSC gave long-term engraftment and differentiation, both in peripheral blood and in lymphoid organs, and production of human antibodies. Vaccinated mice produced specific anti-HER-2 human IgG. An s.c. SK-OV-3 challenge was significantly inhibited (but not abolished) in both vaccinated and non-vaccinated HIS mice. Tumours were heavily infiltrated with human and murine cells, mice showed NK cells and production of human interferon-γ, that could contribute to tumour growth inhibition. Vaccinated HIS mice showed significantly inhibited lung metastases when compared with non-vaccinated HIS mice and to non-HIS mice, along with higher levels of tumour-infiltrating human dendritic cells. CONCLUSION: Anti-HER-2 responses were elicited through an adjuvanted allogeneic cancer cell vaccine in HIS mice. Human immune responses elicited in HIS mice effectively inhibited lung metastases.

A multi-DNA preventive vaccine for p53/Neu-driven cancer syndrome.

The highly aggressive cancer syndrome of female mice carrying a p53 knockout allele and a rat HER-2/neu (Neu) transgene (BALB-p53Neu) can be prevented by a cell vaccine presenting three components: Neu, interleukin (IL)-12 production, and allogeneic major histocompatibility complex (MHC) alleles (Triplex cell vaccine). Here we tested a second-generation Triplex DNA-based vaccine (Tri-DNA), consisting of the combination of three gene components (a transmembrane-extracellular domain fragment of the Neu gene, IL-12 genes, and the H-2D(q) allogeneic MHC gene), carried by separate plasmids. The Tri-DNA vaccine was at least as effective as the Triplex cell vaccine for cancer immunoprevention, giving a similar delay in the onset of mammary cancer and complete protection from salivary cancer. Both vaccines induced anti-Neu antibodies of the murine IgG2a isotype at similar levels. The Tri-DNA vaccine gave more restricted immunostimulation, consisting of a fully helper T cell type 1 (Th1)-polarized response, with effective production of interferon (IFN)-gamma in response to the vaccine but no spontaneous production, and no induction of anti-Neu IgG3 antibodies. On the other hand, the Triplex cell vaccine induced both Th1 and Th2 cytokines, a strong increase in spontaneous IFN-gamma production, and high levels of IgG3 antibodies recognizing Neu-positive syngeneic cells. In conclusion, the Tri-DNA vaccine is as effective as Triplex cell vaccine, exploiting a more restricted immune stimulation.

Toxoplasmosis in pregnancy: research on 2295 women in Rome and its province.

The authors report the data concerning 2295 women tested for toxoplasmosis immunodiagnosis, in the Department of Infectious and Tropical Diseases of "La Sapienza" University of Rome in the years 1993-1994. Four hundred eleven cases (17.9%) were positive for IgG only; 2 cases (0.1%) for IgM only; 15 cases (0.6%) for both IgG and IgM while 1867 cases (81.4%) were negative. 1668 women were pregnant. In this group 260 (15.6%) were positive for IgG only, 2 (0.1%) for IgM only, and 10 (10.6%) for both IgG and IgM; in one case there was a spontaneous absorption in the 10th week of pregnancy, in another case a still-birth in the 20th week with brain lesions; a child was born with phocomelia of the right arm and one with a clubfoot. While it is possible to explain the absorption and the still-birth with the toxoplasma infection, it is difficult to understand the causes of the abnormality of the limbs.

An epidemic of Neisseria gonorrhoeae in a Somali orphanage.

Neisseria gonorrhoeae was isolated from 53 young females (6-14 years old) in a Somali orphanage. A male guardian was found to be the effective transmitter having sexually abused the children. All the bacterial isolates were of the same serogroup WI and the same serovar Aedih. This presents an unusual example of a tight geographic cluster of infected people which is often characteristic of gonorrhoea epidemics.

PIP: The physician of an orphanage in Afgoye, 30 km from Mogadishu, Somalia, noticed vaginal discharge in 95 of the 500 girls at the orphanage in September 1987. A Somali-Italian investigative team took vaginal specimens from the 95 girls. Laboratory personnel isolated Neisseria gonorrhoea in 56% of the 95 6-14 year old females (53) who all lived in 2 adjacent dormitories. They found that all the bacterial isolates were of the N. gonorrhoea WI serogroup and Aedih serovar. The physician prescribed penicillin treatment for all the girls. Contact tracing revealed that a male guardian was the source of gonorrhea. Some children had already accused him of sexually abusing them. Orphanage officials had transferred him 1 week before the arrival of the investigative team. His room had been very near to the 2 dormitories for only a few weeks before the investigative team arrived. In this short time, his sexual abuse effected this cluster of infections. This supports the present theory of gonorrhea epidemiology that a core group of infectious people are most likely responsible for most, if not all, of the continuing endemicity of gonorrhea. The infection rate was in range of the estimated probability of transmission (50-70%) during sexual intercourse from an infectious male to a female. The results showed that high resolution typing of gonococci has in addition to its scientific value a more practical value; forensic medicine and illustration that gonorrhea consists of smaller microepidemics.

Prevalence of anti-HCV in two Tanzanian villages.

The presence of anti-HCV antibodies was investigated in sera from a total of 123 inhabitants of two Tanzanian villages. In one of the villages, 72.2% of the sera and in the other village, 82.6% of the sera were found to be anti-HCV positive. These values are dramatically higher than other reported prevalences, whereby cross-reactivity between HCV and Flaviviruses as well as possible transmission by arthropod vectors cannot be ruled out.