Vaccine procurement and self-sufficiency in developing countries.

This paper discusses the movement toward self-sufficiency in vaccine supply in developing countries (and countries in transition to new economic and political systems) and explains special supply concerns about vaccine as a product class. It traces some history of donor support and programmes aimed at self-financing, then continues with a discussion about self-sufficiency in terms of institutional capacity building. A number of deficiencies commonly found in vaccine procurement and supply in low- and middle-income countries are characterized, and institutional strengthening with procurement technical assistance is described. The paper also provides information about a vaccine procurement manual being developed by the United States Agency for International Development (USAID) and the World Health Organization (WHO) for use in this environment. Two brief case studies are included to illustrate the spectrum of existing capabilities and different approaches to technical assistance aimed at developing or improving vaccine procurement capability. In conclusion, the paper discusses the special nature of vaccine and issues surrounding potential integration and decentralization of vaccine supply systems as part of health sector reform.

Tumor cell retention of antibody Fab fragments is enhanced by an attached HIV TAT protein-derived peptide.

Two peptide analogs of the 37-62 sequence region of the HIV TAT protein bind tightly to the surface of A431 breast carcinoma cells. After conjugation to either of two poorly internalized anti-tumor antibody Fab fragments, the analogs enhanced the in vitro cell surface retention and internalization of the Fab fragments to the level of the whole antibodies. This was at the expense of some binding specificity in the case of 1.6 peptides/NRLU-10 Fab, but not in the case of 1.1 peptides/Fab. Enhanced retention may occur by enhanced bivalent binding of the Fab fragments. The internalized fraction of free peptide, but not of the Fab conjugates, is enhanced by chloroquine. The conjugates which were less specific for tumor cell binding may be useful for enhanced retention/internalization of specifically acting agents, for use at specific sites of injection, or against pre-separated target cell populations, while the more specific conjugate may be of interest for further development.

Enhanced in vitro tumor cell retention and internalization of antibody derivatized with synthetic peptides.

The Fab fragments of two antitumor monoclonal antibodies, NR-ML-05 and NR-LU-10, have been covalently derivatized with synthetic peptides designed to provide secondary sites of attachment to enhance their retention on tumor cells. Analogs of the peptide "GALA", an amphipathic peptide previously reported to interact with uncharged lipid bilayers, gave antibody conjugates of different molecular weight and bound peptide stoichiometry when attached to Fab fragments using the heterobifunctional cross-linker sulfo-SMCC. This attached peptide enhanced the retention and internalization of Fab fragments of NR-ML-05 on FEMX human melanoma cells, but not of NR-LU-10 on HT-29 human colon carcinoma cells, indicating that this effect might be specific for individual tumor antigen-antibody systems. This peptide appeared to increase nonspecific interactions of the conjugate with antigen-negative cells. Other membrane-active peptides were also tested. None were as effective as the "GALA" analogs. A synthetic ion channel peptide attached to NR-ML-05 Fab exhibited the greatest enhanced internalization of these tested peptides.