Efficacy of murine malaria sporozoite vaccines: implications for human vaccine development

As part of a study of potential vaccines against malaria, the protective efficacy of sporozoite subunit vaccines was determined by using the Plasmodium berghei murine malaria model. Mice were immunized with recombinant DNA-produced or synthetic peptide-carrier subunit vaccines derived from the repetitive epitopes of the Plasmodium berghei circumsporozoite gene, or with radiation-attenuated sporozoites. Immunization with subunit vaccines elicited humoral responses that were equivalent to or greater than those elicited by irradiated sporozoites, yet the protection against sporozoite challenge induced by either of the subunit vaccines was far less than that achieved by immunization with attenuated sporozoites. Passive and adoptive transfer studies demonstrated that subunit vaccines elicited predominantly antibody-mediated protection that was easily overcome whereas irradiated sporozoites induced potent cell-mediated immunity that protected against high challenge doses of sporozoites. These studies indicate that new strategies designed to induce cellular immunity will be required for efficacious sporozoite vaccines.     

PrP antibodies do not trigger mouse hippocampal neuron apoptosis

Intraperitoneal administration of ICSM18 and 35, monoclonal antibodies against prion protein (PrP), has been shown to significantly delay the onset of prion disease in mice, and humanized versions are candidate therapeutics for prion and Alzheimer's diseases. However, a previous report of severe and widespread apoptosis after intracerebral injection of anti-PrP monoclonal antibodies raised concerns about such therapy and led to an influential model of prion neurotoxicity via cross-linking of cell surface PrP by disease-related PrP aggregates. In extensive studies including ICSM18 and 35, fully humanized ICSM18, and the previously reported proapoptotic antibodies, we found no evidence of apoptosis, thereby questioning this model of prion neurotoxicity.     

Rationale for development of a synthetic vaccine against Plasmodium falciparum malaria

Protective immunity against malaria can be obtained by vaccination with irradiated sporozoites. The protective antigens known as circumsporozoite (CS) proteins, are polypeptides that cover the surface membrane of the parasite. The CS proteins contain species-specific immunodominant epitopes formed by tandem repeated sequences of amino acids. Here it is shown that the dominant epitope of Plasmodium falciparum is contained in the synthetic dodecapeptide Asn-Ala-Asn-Pro-Asn-Ala-Asn-Pro-Asn-Ala-Pro or (NANP)3. Monoclonal antibodies and most or all polyclonal human antibodies to the sporozoites react with (NANP)3, and polyclonal antibodies raised against the synthetic peptide (NANP)3 react with the surface of the parasite and neutralize its infectivity. Since (NANP)3 repeats are present in CS proteins of P. falciparum from many parts of the world, this epitope is a logical target for vaccine development.     

Effect of antibodies to recombinant and synthetic peptides on P. falciparum sporozoites in vitro

Antibodies were raised in mice immunized with several recombinant and synthetic peptides of the circumsporozoite protein of Plasmodium falciparum. The antibodies were evaluated for protective activity in a human hepatocyte culture system. They exerted their protective effect against the parasite at three points: sporozoite attachment to the hepatocyte surface, entry, and subsequent intracellular development. Inhibition of attachment and entry were found to be related to the antibody titer against the authentic circumsporozoite protein on the sporozoite surface, especially when peptides were administered with alum or complete Freund's adjuvant. Even when invasion was not totally inhibited, the presence of abnormal trophozoites and a frequent inhibition of schizont development in long-term cultures suggested continued activity of antibodies at the intracellular level after sporozoite penetration had been completed.     

Naturally occurring antibodies reactive with sperm proteins: apparent deficiency in AIDS sera

A set of naturally occurring immunoglobulin M (IgM) antibodies that are reactive with a defined subset of proteins in the acrosomal cap region of human sperm has been identified. These antibodies are present in a broad spectrum of human sera from males and females, 1 day to 40 years of age, and are absent or markedly deficient in a large proportion of sera from individuals with the acquired immune deficiency syndrome (AIDS) or at risk for AIDS. The subset of proteins with which the IgM antibodies are reactive includes a factor (or factors) capable of inhibiting lectin-induced T-lymphocyte proliferation. The prevalence of the sperm-reactive IgM antibodies indicates that they are not elicited by sperm. Further, immunoreactivity of the sperm proteins resulting in depletion of specific circulating IgM antibodies, or other interactions between the sperm proteins and elements of the immune system, may be a factor in the suppressed state of the immune system in AIDS.     

Reinnervated eye muscles do not respond to impulses in foreign nerves

Normal movements return to carp eyes after section and regeneration of the IIIrd and IVth nerve trunks. Two months after reinnervation, records of impulses in the inferior oblique nerve during tilting of the body show activity of the normal motoneurons to that muscle, together with discharge patterns characteristic of the antagonistic superior oblique and some of the rectus muscles. These axons must have found their way into the inferior oblique trunk during sprouting at the lesion and must be maintained after reinnervation. Impulses from foreign axons are without detectable effect on eye movement and therefore must be blocked at their termination in the muscle. Previous study of cross-innervated and doubly innervated fish eye muscles revealed only structurally normal neuromuscular junctions. Transmission from foreign junctions in multiply innervated muscle is blocked by competitive molecular recognition and control mechanisms that do not cause degeneration.     

Human monoclonal antibodies to Pf 155, a major antigen of malaria parasite Plasmodium falciparum

Pf 155, a protein of the human malaria parasite Plasmodium falciparum, is strongly immunogenic in humans and is believed to be a prime candidate for the preparation of a vaccine. Human monoclonal antibodies to Pf 155 were obtained by cloning B cells that had been prepared from an immune donor and transformed with Epstein-Barr virus. When examined by indirect immunofluorescence, these antibodies stained the surface of infected erythrocytes, free merozoites, segmented schizonts, and gametocytes. They bound to a major polypeptide with a relative molecular weight of 155K and to two minor ones (135K and 120K), all having high affinity for human glycophorin. The antibodies strongly inhibited merozoite reinvasion in vitro, suggesting that they might be appropriate reagents for therapeutic administration in vivo.     

Vaccinia virus: a tool for research and vaccine development

Vaccinia virus is no longer needed for smallpox immunization, but now serves as a useful vector for expressing genes within the cytoplasm of eukaryotic cells. As a research tool, recombinant vaccinia viruses are used to synthesize biologically active proteins and analyze structure-function relations, determine the targets of humoral- and cell-mediated immunity, and investigate the immune responses needed for protection against specific infectious diseases. When more data on safety and efficacy are available, recombinant vaccinia and related poxviruses may be candidates for live vaccines and for cancer immunotherapy.     

Education to prevent AIDS: prospects and obstacles

A number of obstacles thwart effective education to prevent AIDS in the United States. These include the biological basis and social complexity of the behaviors that must be changed, disagreement about the propriety of educational messages to prevent AIDS, uncertainty about the degree of risk to the majority of Americans, and dual messages of reassurance and alarm from responsible officials. Long-term protection of an individual from infection requires extreme changes in risk-taking behavior. Partial shifts toward safer practices may be epidemiologically important in retarding the rate and extent of spread of infection. Though some striking changes in behavior have occurred, especially in homosexual populations in areas with high prevalence of AIDS, educational efforts to date have succeeded more in raising awareness and knowledge about AIDS than in producing sufficient changes in behavior. The United States has yet to mount a nationwide comprehensive, intensive, and targeted education program to prevent AIDS.     

中国鱼类疫苗技术研发及应用研究进展

随着水产养殖业高密度、规模化、集约化高速发展,病害已成为产业健康可持续发展的重大挑战。鱼类接种疫苗既可以防控水产病害发生、减少产业的经济损失,又可以减少或消除由于大量使用抗生素带来的健康危害、生态风险和水产品食品安全等问题,从而支撑水产养殖业健康、绿色发展。本文综述了目前国内外鱼类疫苗开发中包括灭活疫苗、减毒/弱毒活疫苗、亚单位/合成肽疫苗和DNA疫苗在内的主要技术策略及相应的接种、递送方式,着重介绍了已经获得中国新兽药证书的9个鱼类疫苗及其应用,以及中国鱼类疫苗审批管理的情况。针对中国高效鱼类疫苗品种供给不足和开发进程漫长等问题,提出了未来应加强鱼类病原与病害相关的基础研究、利用多组学技术推进高效鱼类疫苗的分子设计及构建鱼类疫苗工程研究技术平台等鱼类疫苗工程领域的重点研究方向。     

中国鱼类疫苗技术研发及应用研究进展

随着水产养殖业高密度、规模化、集约化高速发展,病害已成为产业健康可持续发展的重大挑战.鱼类接种疫苗既可以防控水产病害发生、减少产业的经济损失,又可以减少或消除由于大量使用抗生素带来的健康危害、生态风险和水产品食品安全等问题,从而支撑水产养殖业健康、绿色发展.本文综述了目前国内外鱼类疫苗开发中包括灭活疫苗、减毒/弱毒活疫...