Protection of macaques against intrarectal infection by a combination immunization regimen with recombinant simian immunodeficiency virus SIVmne gp160 vaccines

We previously reported that immunization with recombinant simian immunodeficiency virus SIVmne envelope (gp160) vaccines protected macaques against intravenous challenge by the cloned homologous virus E11S but that this protection was only partially effective against the uncloned virus, SIVmne. In the present study, we examine the protective efficacy of this immunization regimen against infection by a mucosal route. We found that the same gp160-based vaccines were highly effective against intrarectal infection not only with the E11S clone but also with the uncloned SIVmne. Protection against mucosal infection is therefore achievable by parenteral immunization with recombinant envelope vaccines. Protection appears to correlate with high levels of SIV-specific antibodies and, in animals protected against the uncloned virus, the presence of serum-neutralizing activities. To understand the basis for the differential efficacies against the uncloned virus by the intravenous versus the intrarectal routes, we examined viral sequences recovered from the peripheral blood mononuclear cells of animals early after infection by both routes. We previously showed that the majority (85%) of the uncloned SIVmne challenge stock contained V1 sequences homologous to the molecular clone from which the vaccines were made (E11S type), with the remainder (15%) containing multiple conserved changes (the variant types). In contrast to intravenously infected animals, from which either E11S-type or the variant type V1 sequences could be recovered in significant proportions, animals infected intrarectally had predominantly E11S-type sequences. Preferential transmission or amplification of the E11S-type viruses may therefore account in part for the enhanced efficacy of the recombinant gp160 vaccines against the uncloned virus challenge by the intrarectal route compared with the intravenous route.     

Assessment of the effectiveness of different methoods of immunization with live plague vaccine EB in aerosol infections]

The work deals with the results of the comparative evaluation of the effectiveness of vaccines developed at the Sanitary Research Institute (Zagorsk) and the Mechnikov Research Institute for Vaccines and Sera (Moscow), as well as two methods of immunization against plague, by inhalation and subcutaneous injection, under the conditions of aerosol infection. The immunogenic effectiveness of both vaccines, when evaluated in terms of LD50, was shown to be approximately the same, but the animals immunized by the inhalation method with the vaccine developed at the Sanitary Research Institute proved to be less susceptible to infection than those immunized with the vaccine developed at the Mechnikov Research Institute for Vaccines and Sera in Moscow. After immunization by the inhalation method the vaccine developed at the Sanitary Research Institute rendered more effective protection (3- to 4-fold) against aerosol infection than after immunization by subcutaneous injection. The animals immunized by the inhalation method proved to be capable of surviving plague in the primary pneumonic form.     

Vaccination strategies against Tritrichomonas foetus

Immunoprophyloxis for bovine trichomoniosis has been a priority because of the high prevalence o f the disease, the considerable economic loss due to the infection and the lack of approved chemotherapeutic agents. The commercial availability of first-generation vaccines provides hope not only for even more effective immunization regimens far this disease, but also for other protozoal infections and for sexually transmitted diseases (STDs) caused by a wide variety of infectious agents. At present, efficacious vaccines for protozoal diseases and for STDs are rare. Since information gained on immunization against Tritrichomonas foetus may have broad significance for control of these two classes of infection,it is important to explore the biological basis of protection against this protozoal infection of the reproductive tract In this paper, Lynette Corbeil reviews data on host-parasite relationships in bovine trichomoniasis as a basis for developing vaccine strategies.     

Leptospirosis vaccines

Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP) vaccines, lipopolysaccharide (LPS) vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.     

Development of recombinant antigen vaccines for the control of theileriosis

Immunization against Theileria parva involves infection with sporozoites and simultaneous treatment with a long-acting tetracycline. For T. annulata, immunization is achieved by inoculation of attenuated schizont-infected lymphocytes. The two methods are inadequate because of the use of live organisms and the methods are also bedevilled by the multiplicity of strains, particularly of T. parva. For these reasons, alternative methods of control are being sought. In this review an attempt is made to highlight advances towards subunit vaccines against T. parva and T. annulata. Several candidate antigens which are thought to induce protective responses have been identified and recombinant DNA technology is being employed to produce these antigens in bulk. Relevant antigens may be delivered as subunit vaccines by using recombinant vaccinia virus or attenuated Salmonella spp. as carriers of the genes expressing these antigens. It is likely that effective vaccines against T. parva and T. annulata will have to elaborate immune responses against both the sporozoite and schizont stages of the parasite.     

Overview of vaccines and vaccination

Of the 80-plus known infectious agents pathogenic for humans, there are now more than 30 vaccines against 26 mainly viral and bacterial infections and these greatly minimize subsequent disease and prevent death after exposure to those agents. This article describes the nature of the vaccines, from live attenuated agents to subunits, their efficacy and safety, and the kind of the immune responses generated by those vaccines, which are so effective. To date, all licensed vaccines generate especially specific antibodies, which attach to the infectious agent and therefore can very largely prevent infection. These vaccines have been so effective in developed countries in preventing mortality after a subsequent infection that attempts are being made to develop vaccines against many of the remaining infectious agents. Many of the latter are difficult to manipulate; they can cause persisting infections or show great antigenic variation. A range of new approaches to improve selected immune responses, such as immunization with DNA or chimeric live vectors, viral or bacterial, are under intense scrutiny, as well as genomic analysis of the agent.     

Experimental study of vaccines against Salmonella typhimurium infection.

Serological and protective activities of vaccines from S. typhimurium and S. minnesota were studied. It has been demonstrated that active protection against infection in experimental salmonellosis in mice can only be obtained by immunization of the animals using vaccines from complete antigenic complexes isolated from S-strains. It has been found that expressed anti-infection immunity (unlike anti-endotoxic immunity) is induced to the same extent by either high-molecular components (2,000,000 daltons and more), showing great serological activity, or components with relatively low molecular weight (15,000--20,000 daltons) and minimum serological activity. Vaccines from Ra- and Re-strains of S. minnesota do not induce resistance to S. typhimurium infection in mice in either active protection tests or passive protection tests.     

Complete Protection of Mice against Lethal Murine Cytomegalovirus Challenge by Immunization with DNA Vaccines Encoding Envelope Glycoprotein Complex III Antigens gH,gL and gO

Human cytomegalovirus infects the majority of humanity which may lead to severe morbidity and mortality in newborns and immunocompromised adults. Humoral and cellular immunity are critical for controlling CMV infection. HCMV envelope glycoprotein complexes (gC I, II, III) represent major antigenic targets of antiviral immune responses. The gCIII complex is comprised of three glycoproteins, gH, gL, and gO. In the present study, DNA vaccines expressing the murine cytomegalovirus homologs of the gH, gL, and gO proteins were evaluated for protection against lethal MCMV infection in the mouse model. The results demonstrated that gH, gL, or gO single gene immunization could not yet offer good protection, whereas co-vaccination strategy apparently showed effects superior to separate immunization. Twice immunization with gH/gL/gO pDNAs could provide mice complete protection against lethal salivary gland-derived MCMV (SG-MCMV) challenge, while thrice immunization with pgH/pgL, pgH/pgO or pgL/pgO could not provide full protection. Co-vaccination with gH, gL and gO pDNAs elicited robust neutralizing antibody and cellular immune responses. Moreover, full protection was also achieved by simply passive immunization with anti-gH/gL/gO sera. These data demonstrated that gCIII complex antigens had fine immunogenicity and might be a promising candidate for the development of HCMV vaccines.     

抵抗女性生殖道沙眼衣原体感染的免疫新策略

沙眼衣原体是引起沙眼和泌尿生殖道感染的主要病原体。据世界卫生组织2015年统计,全球每年约有1.3亿沙眼衣原体感染新发病例。研究表明CD4^+Th1型细胞免疫应答在抵抗沙眼衣原体感染中发挥着重要作用。因此,研究者依照抗沙眼衣原体感染的免疫应答特点,构建出许多候选疫苗,但都没有成功地应用于临床。近年研究发现,生殖道黏膜组织不仅存在体液免疫和细胞免疫,还驻留着一些引人注目的免疫细胞,提示增强黏膜免疫可作为预防沙眼衣原体感染的潜在途径,是抵抗生殖道沙眼衣原体感染的免疫新策略。本文全面概述了黏膜免疫与女性生殖道沙眼衣原体感染的研究进展,并为今后研制沙眼衣原体疫苗提供一些建议。     

Vaccination of children born from HIV-infected mothers against Haemophilus influenzae type b infection

Course of postvaccinal period after injection of vaccine against Haemophilus influenzae type b administered simultaneously with vaccines of Russian national immunization schedule was studied in children born from HIV-infected mothers. Good tolerability of the vaccine administered concomitantly with diphtheria-tetanus-whole cell pertussis and inactivated polio vaccines (Imovax Polio), which is comparable with tolerability in healthy children, was demonstrated. Prevaccination titers of antibodies and their dynamics during immunization process were described. Increase of levels of antibodies was detected both in the group of children with perinatal contact with HIV infection and in the group of HIV-infected children.     

Serotype-independent protection against pneumococcal infections elicited by intranasal immunization with ethanol-killed pneumococcal strain,SPY1

The 23-valent polysaccharide vaccine and the 7-valent pneumococcal conjugate vaccine are licensed vaccines that protect against pneumococcal infections worldwide. However, the incidence of pneumococcal diseases remains high in low-income countries. Whole-cell vaccines with high safety and strong immunogenicity may be a favorable choice. We previously obtained a capsule-deficient Streptococcus pneumoniae mutant named SPY1 derived from strain D39. As an attenuated live pneumococcal vaccine, intranasal immunization with SPY1 elicits broad serotype-independent protection against pneumococcal infection. In this study, for safety consideration, we inactivated SPY1 with 70% ethanol and intranasally immunized BALB/c mice with killed SPY1 plus cholera toxin adjuvant for four times. Results showed that intranasal immunization with inactivated SPY1 induced strong humoral and cellular immune responses. Intranasal immunization with inactivated SPY1 plus cholera toxin adjuvant elicited effective serotype-independent protection against the colonization of pneumococcal strains 19F and 4 as well as lethal infection of pneumococcal serotypes 2, 3, 14, and 6B. The protection rates provided by inactivated SPY1 against lethal pneumococcal infection were comparable to those of currently used polysaccharide vaccines. In addition, vaccine-specific B-cell and T-cell immune responses mediated the protection elicited by SPY1. In conclusion, the 70% ethanol-inactivated pneumococcal whole-cell vaccine SPY1 is a potentially safe and less complex vaccine strategy that offers broad protection against S. pneumoniae.     

Untersuchungen zur Oberfläuchenstruktur von Pasteurella multocida

Detailed studies of the surface structures are an important requirement for the development of efficient vaccines against enzootic pneumonia in calves and piglets caused by Pasteurella multocida. Electron microscopical examination after Alcian Blue staining shows capsular material extending far into the surrounding medium. The extent of the capsules depicted by light microscopy did not correlate with virulence and immunogenicity. However, the extent of the capsules was effected by different culture conditions. The immunization with extract material resulted in a good protection against homologous infection. It has been shown that different cultivation conditions can result in heterogeneity of LPS and in altered OMP-profiles.     

Efficacy of Pertussis Vaccines: A Brighter Horizon

A study of pertussis infections in 186 children under 11 years of age in the Manchester region during 1969-71 suggests that recently-manufactured vaccines have been more effective than those made before 1967. The earlier vaccines were effective mainly against the serotypes of Bordetella pertussis possessing antigen 2, while those made from 1967 are more nearly equal in their effectiveness against thedi fferent serotypes. A booster dose of the earlier vaccines did not prevent infection with type 1,3 organisms, but we obtained a positive culture from only one child who had received four doses of recent vaccine.Simultaneous infection of a child with two or more serotypes was frequently seen. The predominant serotype in a patient was usually type 1,3; less often it was type 1,2,3 or type 1,2; it was never type 1. A change of serotype sometimes occurs during the course of the illness and is probably directed by the vaccination status of the patient in relation to the serotype of the initial infection.Our findings emphasize the need for vaccines to contain adequate amounts of all three pertussis agglutinogens, and for satisfactory immunization schedules to be used in their administration.     

A recombinant influenza A virus expressing domain III of West Nile virus induces protective immune responses against influenza and West Nile virus

West Nile virus (WNV) continues to circulate in the USA and forms a threat to the rest of the Western hemisphere. Since methods for the treatment of WNV infections are not available, there is a need for the development of safe and effective vaccines. Here, we describe the construction of a recombinant influenza virus expressing domain III of the WNV glycoprotein E (Flu-NA-DIII) and its evaluation as a WNV vaccine candidate in a mouse model. FLU-NA-DIII-vaccinated mice were protected from severe body weight loss and mortality caused by WNV infection, whereas control mice succumbed to the infection. In addition, it was shown that one subcutaneous immunization with 10(5) TCID(50) Flu-NA-DIII provided 100% protection against challenge. Adoptive transfer experiments demonstrated that protection was mediated by antibodies and CD4+T cells. Furthermore, mice vaccinated with FLU-NA-DIII developed protective influenza virus-specific antibody titers. It was concluded that this vector system might be an attractive platform for the development of bivalent WNV-influenza vaccines.     

综述与专论: 针对严重急性呼吸综合征冠状病毒2变异株Omicron的疫苗研究进展

2021年底,严重急性呼吸综合征冠状病毒2 Omicron变异株迅速取代Delta突变株在世界范围内广泛流行,其S蛋白具有36个位点突变,导致致病力和传播力发生明显变化,并且具备了免疫逃逸的能力。疫苗接种是目前疫情防控最普适的手段,研究发现,现有疫苗针对Omicron突变株的保护效果明显下降。新的免疫策略或特异性疫苗/多价疫苗针对Omicron有效性的评估均需要动物模型的支撑。在实验室条件下,利用动物模型进行活病毒攻击实验,是在体内验证保护性中和抗体、疫苗有效性的关键技术手段,本文将从动物模型方向综述国内外针对Omicron变异株的疫苗研究进展。     

Corynebacterium parvum as an adjuvant for Trypanosoma cruzi epimastigote vaccines: a comparison with saponin and Bordetella pertussis.

The effect was compared in CBA mice of adding Corynebacterium parvum, saponin, and Bordetella pertussis to living or killed Trypanosoma cruzi (Y strain) epimastigote vaccines on the induction of protective immunity against subcutaneous (s.c.) challenge with blood trypomastigotes. The addition of C. parvum to a low dose of T. cruzi vaccine, which alone was non-protective, generated a greater degree of protection than did saponin or B. pertussis. C. parvum alone increased resistance to infection to a variable and usually weak extent. The addition of C. parvum to larger doses of T. cruzi vaccine, which were themselves sufficient to elicit some degree of protection, improved resistance when the challenge was given 1 or 12 weeks after immunization, but lowered it at 3 weeks. It is concluded that the comparative efficacy of adjuvants for T. cruzi vaccines needs to be assessed on 3 parameters: (1) the dose of antigen, (2) the dose of adjuvant and (3) the time interval between immunization and challenge.     

Enhancement of feline immunodeficiency virus (FIV) infection after DNA vaccination with the FIV envelope.

Despite intensive experimentation to develop effective and safe vaccines against the human immunodeficiency viruses and other pathogenic lentiviruses, it remains unclear whether an immune response that does not afford protection may, on the contrary, produce adverse effects. In the present study, the effect of genetic immunization with the env gene was examined in a natural animal model of lentivirus pathogenesis, infection of cats by the feline immunodeficiency virus (FIV). Three groups of seven cats were immunized by intramuscular transfer of plasmid DNAs expressing either the wild-type envelope or two envelopes bearing mutations in the principal immunodominant domain of the transmembrane glycoprotein. Upon homologous challenge, determination of plasma virus load showed that the acute phase of viral infection occurred earlier in the three groups of cats immunized with FIV envelopes than in the control cats. Genetic immunization, however, elicited low or undetectable levels of antibodies directed against envelope glycoproteins. These results suggest that immunization with the FIV env gene may result in enhancement of infection and that mechanisms unrelated to enhancing antibodies underlay the observed acceleration.     

Combining liver- and blood-stage malaria viral-vectored vaccines: investigating mechanisms of CD8+ T cell interference

Replication-deficient adenovirus and modified vaccinia virus Ankara (MVA) vectors expressing single pre-erythrocytic or blood-stage Plasmodium falciparum Ags have entered clinical testing using a heterologous prime-boost immunization approach. In this study, we investigated the utility of the same immunization regimen when combining viral vectored vaccines expressing the 42-kDa C terminus of the blood-stage Ag merozoite surface protein 1 and the pre-erythrocytic Ag circumsporozoite protein in the Plasmodium yoelii mouse model. We find that vaccine coadministration leads to maintained Ab responses and efficacy against blood-stage infection, but reduced secondary CD8(+) T cell responses against both Ags and efficacy against liver-stage infection. CD8(+) T cell interference can be minimized by coadministering the MVA vaccines at separate sites, resulting in enhanced liver-stage efficacy in mice immunized against both Ags compared with just one. CD8(+) T cell interference (following MVA coadministration as a mixture) may be caused partly by a lack of physiologic space for high-magnitude responses against multiple Ags, but is not caused by competition for presentation of Ag on MHC class I molecules, nor is it due to restricted T cell access to APCs presenting both Ags. Instead, enhanced killing of peptide-pulsed cells is observed in mice possessing pre-existing T cells against two Ags compared with just one, suggesting that priming against multiple Ags may in part reduce the potency of multiantigen MVA vectors to stimulate secondary CD8(+) T cell responses. These data have important implications for the development of a multistage or multicomponent viral vectored malaria vaccine for use in humans.     

Antibody Response and Protection Induced by Immunization with Smooth and Rough Strains in Experimental Salmonellosis

The antibody response of mice to a smooth strain of Salmonella typhimurium was shown previously to be extremely rapid and potent. As measured by the complement-mediated bactericidal reaction, it was also found to be highly specific as well as reproducible. Experiments which studied the effects of antigen type (live or heat-killed), antigen dose, and the route of immunization indicated that the most rapid and highest antibody response was achieved with live, smooth organisms injected by the intraperitoneal route. Living vaccines of rough strains of either S. typhimurium or S. enteritidis induced antibodies directed against the corresponding smooth organisms. The response to the rough strains was apparently due to antibody production rather than to the simple release of preformed natural antibody. The duration of protection conferred by the rough strain vaccines was closely correlated with the endotoxic content of the immunizing strain. Smooth heat-killed vaccines and a rough live vaccine protected against homologous but not heterologous challenge. In contrast, immunization with a smooth live vaccine protected mice against both homologous and heterologous challenge infections. Protection was not due to a local effect in the peritoneal cavity, since mice were also protected against subcutaneous challenge. The secondary antibody response, induced in immunized animals by the virulent challenge infection, was demonstrated to be rapid and potent, and hence a factor to be considered in protection.