Strategies for developing vaccines against H5N1 influenza A viruses

Recent outbreaks of highly pathogenic avian influenza A virus (H5N1 subtype) infections in poultry and humans (through direct contact with infected birds) have raised concerns that a new influenza pandemic might occur in the near future. Effective vaccines against H5N1 virus are, therefore, urgently needed. Reverse-genetics-based inactivated vaccines have been prepared according to World Health Organization (WHO) recommendations and are now undergoing clinical evaluation in several countries. Here, we review the current strategies for the development of H5N1 influenza vaccines, and future directions for vaccine development.     

AIDS: acquired immunodeficiency syndrome

Acquired immunodeficiency syndrome, or AIDS, is a new illness that occurs in previously healthy individuals. It is characterized by immunodeficiency, opportunistic infections and unusual malignant diseases. Life-threatening single or multiple infections with viruses, mycobacteria, fungi or protozoa are common. A rare neoplasm, Kaposi''s sarcoma, has developed in approximately one third of patients with AIDS. More than 800 cases of AIDS have been reported in North America, over 24 of them in Canada. The majority of patients are male homosexuals, although AIDS has also developed in abusers of intravenously administered drugs, Haitian immigrants, individuals with hemophilia, recipients of blood transfusions, prostitutes, and infants, spouses and partners of patients with AIDS. The cause of AIDS is unknown, but the features are consistent with an infectious process. Early diagnosis can be difficult owing to the nonspecific symptoms and signs of the infections and malignant diseases. Therefore, vigilance by physicians is of the utmost importance.     

Microsporidia and acquired immunodeficiency syndrome

Microsporidia is a common term that has been used to refer to a group of eukaryotic, obligate intracellular protozoan parasites belonging to the phylum Microspora. They are important agricultural parasites, contaminating commercial insects; they are also important by infecting laboratory rodents, rabbits and primates. Ever since the early cases found by Magarino Torres, who reported the presence of Encephalitozoon in a patient suffering of a meningoencephalomyelitis, some human pathology caused by microsporidia has been described. However, only after the acquired immunodeficiency syndrome outbreak have these organisms appeared as significant etiological agents in different pathologies. Even so, they remain underestimated. In the present article, the importance of microsporidia for the human pathology in immunocompromised host has been stressed.     

Nutrition and infectious diseases in developing countries and problems of acquired immunodeficiency syndrome

Infectious diseases are the major causes of death and morbidity in underdeveloped countries, particularly in children. Increasing evidence suggests that malnutrition-both Protein-Energy type Malnutrition (PEM) and essential micronutrient (vitamins, trace minerals, essential amino acids, polyunsaturated fatty acids) type-is the underlying reason for increased susceptibility to infections. On the other hand, certain infectious diseases also cause malnutrition, which results in a vicious cycle. Before its viral origin was known, acquired immunodeficiency syndrome (AIDS) had been termed the thin disease because cachexia was AIDS' main clinical manifestation. The relationship between infection and malnutrition is well documented in the literature. Our experience supports this. Preventive and therapeutic measures are suggested.     

AIDS: acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome, or AIDS, is a new illness that occurs in previously healthy individuals. It is characterized by immunodeficiency, opportunistic infections and unusual malignant diseases. Life-threatening single or multiple infections with viruses, mycobacteria, fungi or protozoa are common. A rare neoplasm, Kaposi''s sarcoma, has developed in approximately one third of patients with AIDS. More than 800 cases of AIDS have been reported in North America, over 24 of them in Canada. The majority of patients are male homosexuals, although AIDS has also developed in abusers of intravenously administered drugs, Haitian immigrants, individuals with hemophilia, recipients of blood transfusions, prostitutes, and infants, spouses and partners of patients with AIDS. The cause of AIDS is unknown, but the features are consistent with an infectious process. Early diagnosis can be difficult owing to the nonspecific symptoms and signs of the infections and malignant diseases. Therefore, vigilance by physicians is of utmost importance.     

艾滋病免疫重建治疗策略的研究进展

获得性免疫缺陷综合征( AIDS) 是由人类免疫缺陷病毒( HIV) 侵犯并破坏机体免疫系统引起的疾病。20 世纪90 年代前, 人们普遍认为免疫系统的破坏是不可逆转的, 但自高效抗反转录病毒疗法出现以后, 发现受损的免疫功能可以获得重建并成为研究的热点。免疫功能重建是指患者受损的免疫功能恢复到正常水平或接近正常水平, 从而降低机会性感染和肿瘤的发生, 降低发病率和病死率。随着各项技术的发展和改进, AIDS 的发病机制和免疫重建机制得到进一步研究, 改善调节患者CD4⁺细胞的数量和免疫功能及细胞毒性T细胞( CTL) 的杀伤功能是最重要的保护性免疫机制。目前一些治疗新策略和手段, 如细胞因子治疗、HIV 特异性疫苗的研制已进入试验或临床阶段, 以期进一步改善患者的免疫功能。     

Ocular complications of the acquired immunodeficiency syndrome

The acquired immunodeficiency syndrome (AIDS) affects the ocular structures in several ways. Kaposi's sarcoma has been observed on the bulbar conjunctiva of the globe. Retinal complications, however, are of major concern. Cotton-wool spots are commonly seen in AIDS patients and are usually of no consequence, except that they must be distinguished from the early stages of cytomegalovirus (CMV) retinitis, seen in 20-40% of these patients. CMV causes a necrotic-type retinitis potentially leading to blindness. 9-[2-Hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine (DHPG) has been found effective in the short-term treatment of this disorder. It is planned to use AS101 in the regimen to see if a long-term cure from this disease can be affected. Care must be taken in handling ocular tissue of AIDS patients or the re-use of ophthalmic instruments touching the eye of AIDS patients since the human immunodeficiency virus has been found in these structures.     

Pulmonary complications of the acquired immunodeficiency syndrome

Cardiac transplantation has evolved from an experiment to an accepted therapy for severe heart failure. Increasing competition for donor organs mandates a greater emphasis on selection and timing for transplantation and paradoxically forces more reliance on aggressive medical therapy for all patients after evaluation. The growth of recipient and donor pools may enhance the opportunity for assessing histocompatibility, for which distinguishing between autoantibodies and human leukocyte antigen-determined reactivity is important, and some general nonresponders may be detected. Therapy with cyclosporine has improved the outcome after transplantation, but further refinement is needed, perhaps with pharmacologic synergy, to minimize nephrotoxicity and maximize specific immunosuppression. Survival is more than 80% at 1 year, after which the incidence of acute rejection and infection declines and accelerated atherosclerosis becomes prominent. Although resuming employment is not always possible, the overall quality of life is excellent after cardiac transplantation.     

Immunological memory and acquired immunodeficiency syndrome pathogenesis

Infection with the human immunodeficiency virus results in profound perturbations in immunological memory, ultimately resulting in increased susceptibility to opportunistic infections and acquired immunodeficiency syndrome (AIDS). We have used rhesus macaques infected with the simian immunodeficiency virus (SIV) as a model to understand better the effects of AIDS virus infection on immunological memory. Acute infection with SIV resulted in significant deficits in CD4+ helper responses to cytomegalovirus (CMV) as well as CMV-specific cytotoxic T-lymphocyte and neutralizing antibody responses. Reactivation of CMV was associated with high levels of SIV replication and suppression of both T-helper and cytotoxic responses to CMV. We have also studied the effects of SIV infection on T-cell turnover in non-human primates. T-cell turnover was evaluated using the nucleoside analogue bromodeoxyuridine (BrdU) in combination with five-colour flow cytometric analysis. T cells in normal animals turned over at relatively rapid rates, with memory cells turning over more quickly than naive cells. In SIV-infected animals, the labelling and elimination rates of both CD4+ and CD8+ BrdU-labelled cells were increased by two- to threefold compared with normal controls. Further analysis of immunological memory in non-human primates should offer the opportunity to extend immunological insights from murine models to the pathogenesis and prevention of AIDS.     

Serological response against Mycobacterium avium complex glycolipid antigens in patients with acquired immunodeficiency syndrome

In 43 MAC infected patients (23 non-HIV and 20 AIDS) the IgG response against 3 BCG and 2 MAC antigens was assessed. The response to four antigens in patients with AIDS was considerably lower than in non-HIV infected patients. Therefore, antibody production against MAC glycolipid antigens was impaired in AIDS patients.     

Use of Old World monkeys for acquired immunodeficiency syndrome research

Mangabeys, macaques, and baboons persistently infected with human immunodeficiency virus (HIV)-2 NIH-DZ demonstrated no signs of immunodeficiency disease after 6-11 months following seroconversion. Thus Old World monkeys provide an animal model to investigate the effects of passive immunization (anti-HIV-2 antibodies) on HIV infection in primates.     

Experimental oral polio vaccines and acquired immune deficiency syndrome

The simian immunodeficiency virus (SIV) of the common chimpanzee is widely acknowledged as the direct ancestor of HIV-1. There is increasing historical evidence that during the late 1950s, kidneys were routinely excised from central African chimpanzees by scientists who were collaborating with the polio vaccine research of Dr Hilary Koprowski, and sent - inter alia - to vaccine-making laboratories in the USA and Africa, and to unspecified destinations in Belgium. While there is no direct evidence that cells from these kidneys were used as a substrate for growing Dr Koprowski's oral polio vaccines, there is a startling coincidence between places in Africa where his CHAT vaccine was fed, and the first appearances in the world of HIV-1 group M and group-M-related AIDS. Because of the enormous implications of the hypothesis that AIDS may be an unintended iatrogenic (physician-caused) disease, it is almost inevitable that this theory will engender heated opposition from many of those in the scientific establishment, and those with vested interests.     

Paracoccidioidomycosis in a patient with acquired immunodeficiency syndrome

The authors report a case of paracoccidioidomycosis and other opportunistic diseases in a patient with acquired immunodeficiency syndrome.