Vaccination Of Men Research Articles

A virus-based vaccine may prevent cervical cancer

High-risk human papillomaviruses (HPVs) are now recognized as the etiologic agents of invasive cervical cancer, a major cancer in women. A single HPV type (type 16) is responsible for about 50% of the cancers. The major capsid protein of papillomaviruses, L1, when expressed by recombinant DNA technology, has the intrinsic ability to assemble into virus-like particles (VLPs). In a recent study, a vaccine based on HPV 16 VLPs was tested in a placebo-controlled proof-of-principle trial in young women in the United States. The vaccine was found to prevent 100% of incident persistent HPV 16 infections and HPV 16-associated cervical intraepithelial neoplasia. These results offer promise that cervical cancer will be preventable by an HPV-based vaccine. Studies planned or in progress are examining the efficacy of the vaccine in men, in HIV-infected individuals, and in other parts of the world. Attempts are being made to prepare vaccines that can be administered more easily to large populations.

Non-responsiveness to hepatitis B surface antigen vaccines is not caused by defective antigen presentation or a lack of B7 co-stimulation

The mechanisms causing non-responsiveness to hepatitis B surface antigen (HBsAg) vaccines in man remain elusive. The increased incidence of non-responsiveness in subjects with HLA-DR3(+) or -DR7(+) haplotypes suggests that immune response mechanisms governed by genes of the MHC are involved. Homozygotes for these two haplotypes are found almost exclusively in the non-responder (NR) population. It is conceivable that antigen-presenting cells (APC) of NR are defective in the uptake of HBsAg and that they are unable to present this Ag adequately. Previously, we demonstrated that DR2(+), DR7(+) and DP4(+) NR were able to present HBsAg. In the present paper we demonstrate that six DR0301(+) NR, five of which are homozygous for this marker, were able to take up, process and present HBsAg to HBsAg-specific, DR0301-restricted T cell lines. Non-fractionated peripheral blood mononuclear cells (PBMC) from the DR0301(+) NR did not proliferate to HBsAg in vitro, whereas they proliferated vigorously upon stimulation with tetanus toxoid, thus ruling out the presence of a generalized immunodeficiency. We therefore conclude that HLA-DR0301(+) NR vaccinees are not deficient in their HBsAg-presentation. Because it was demonstrated that recently activated T cells can apparently bypass the requirement for B7, we may have overlooked the role of the B7-co-stimulation in our set-up that used HBsAg-specific T cell lines. Therefore we examined the expression of B7 co-stimulatory molecules on NR-APC. CD86 was normally present on these cells and was not down-regulated after culturing the PBMC in the presence of HBsAg. We conclude that CD86 expression on CD14(+) monocytes of DR0301- and DR07-homozygous poor responders is not deficient and cannot be the mechanism underlying the non-responsiveness of these subjects.

The kinetics of the systemic and local immune response to parenteral influenza vaccination

Studying the humoral immune response after influenza vaccination, with focus on the immune activity occurring locally at mucosal surfaces and in associated lymphoid tissue, provides a valuable tool for understanding immunity to influenza. Here we summarize our work addressing the kinetics of the local and the systemic immune responses after influenza vaccination in humans. Our studies have shown that inactivated influenza vaccine induced a rapid systemic immune response, which was associated with a local response in tonsils and oral fluid in healthy adults. However, the response in tonsils and oral fluid was impaired in young children (under 3 years old). The rapidity and the magnitude of the immune response did not seem to be impaired in diabetic patients and was not altered by treatment of healthy adults with the antiviral zanamivir. High frequencies of influenza-specific antibody secreting cells (ASC) were detected in nasal mucosa of healthy adults. However, parenteral vaccination did not induce an increase in frequency or the number of these ASC. Ongoing studies are investigating the characteristics of influenza-specific T- and B-cells induced locally and systemically after vaccination in man.

Vaccination against Leishmania infections.

Leishmaniasis, that affects millions of people worldwide, is an infectious disease caused by the protozoan parasite Leishmania. Incidence of the condition appears to be increasing in several parts of the world. Of the three main presentations of the disease, i.e. cutaneous, mucocutaneous and visceral, only the first one tends to heal spontaneously, while the other two are considered fatal if left to run their natural course. Recovery from leishmaniasis, whether spontaneous or drug-induced, is usually accompanied by solid immunity against reinfection, which provides a rationale for attempting to design vaccines against the disease. This review presents an outline of the main immunological features of Leishmania infections and of the mechanisms thought to operate in recovery from the disease. It describes various experimental approaches to vaccination in man and animal models, including the use of virulent and avirulent organisms, of dead parasites and extracts thereof, and of purified parasite proteins. Assays using novel technologies, such as the direct injection of DNAs encoding parasite proteins, or the inoculation of viral or bacterial vectors expressing such molecules, as well as recent experiments aimed at inducing an immune response against saliva of the insect vector, are also reviewed. Observations made during the course of these studies have reinforced the notion that vaccination against leishmaniasis is indeed feasible. However, in spite of intensive efforts by many groups and many reports of success in man and in animal models, a consensus is yet to emerge as to what constitutes the best approach to vaccination against leishmaniasis.

Vaccines against dangerous pathogens.

Dangerous pathogens are defined by the UK Health and Safety Executive's advisory committee as category 3 (those which cause severe human disease for which prophylaxis or therapy is usually available) or category 4 (as for category 3, but for which prophylaxis or therapy is not available). Research and development of vaccines for such pathogens is challenging, due to the safety constraints in the manipulation of these pathogens. This chapter discusses the various approaches which can be taken to develop candidate vaccines for these pathogens, including the potential impact of genome sequencing on shortening the time required for R&D. For these pathogens, a direct test of the efficacy of the candidate vaccines in man is not ethical and, therefore, particular emphasis is placed on the demonstration of efficacy in animal models. Emphasis is also placed on the derivation of surrogate markers of efficacy and a demonstration that these correlate with protection in the animal model.

Understanding correlates of hepatitis B virus vaccination in men who have sex with men: what have we learned?

Understanding correlates of hepatitis B virus vaccination in men who have sex with men: what have we learned?

Intra-nasal infection of macaques with Yellow Fever (YF) vaccine strain 17D: a novel and economical approach for YF vaccination in man

Investigating new and simple application routes for YF vaccine, four groups of 4–6 rhesus monkeys were vaccinated with live attenuated 17D YF-vaccine. In two groups the vaccine was administered either as spray into the oral cavity, or as an encapsulated form directly into the stomach. Only one out of eight animals developed a humoral immune response against 17D. In the third group receiving the vaccine intranasally by spray and in the fourth group serving as control all ten monkeys developed an immune response. From all except one of these seroconverted monkeys virus could be detected either by virus reisolation or RT-PCR. All these animals showed a serological immune response in immunofluorescence and neutralisation test. Parallel to viremia, an increase of neopterin as an unspecified immune activation marker could be demonstrated for these animals. Intra-nasal application of 17D-vaccine seems to be a good alternative to subcutaneous immunisation in mass vaccination campaigns.

Awareness and Utilization of the Hepatitis B Vaccine Among Young Men in the Ann Arbor Area Who Have Sex With Men

The authors conducted a preliminary assessment of hepatitis B vaccination rates among men 18- to 37-years-old who have sex with men in a college town to determine what proportion were willing to be vaccinated. Participants, who were sampled in gay bars, gay advocacy groups, a swim team, and a dance club, completed a 25-item questionnaire. Sixty-seven percent were aware of the hepatitis B vaccine, yet only 22% had received the full series of three injections; only 37% had been tested for the virus. On a scale of 1 to 10 for willingness to be vaccinated (10 being most willing), 58% indicated a 10 (M = 8.5). Thirty percent indicated they received safer sex information from university health services, and 14% reported they had received hepatitis B vaccination information there. Hepatitis B vaccination of men who have sex with men in college towns should be a high priority for university health services.

The effect of immunization with inactivated hepatitis A vaccine on the clinical course of HIV-1 infection: 1-year follow-up.

To determine the long-term safety of inactivated hepatitis A virus (HAV) vaccine in men infected with HIV-1. A 1-year prospective case-control study. Targeted primary care and sexually transmitted diseases clinics. Ninety HIV-1-positive patients who participated in an earlier efficacy study of HAV vaccination. Ninety HIV-1-positive men, matched for CD4+ lymphocyte percentage at baseline, who did not receive HAV vaccine. All cases were assigned to receive two intramuscular doses of 1440 enzyme-linked immunosorbent assay units of inactivated HAV vaccine (Havrix) either 1 or 6 months apart. Development of AIDS, survival, and T-cell subsets after 1 year of follow-up. No significant differences were seen between cases and control for the development of AIDS (10.1 versus 10.7%), deaths (7.3 versus 7.6%) nor for mean decline in circulating CD4+ lymphocyte count (125 versus 123 x 10(6)/1) after 1 year. Vaccination against HAV appears to be safe in the longer term for HIV-1-infected men.

Whole-Body Protein Turnover and Hepatic Protein Synthesis Are Increased by Vaccination in Man

1. The ability of diphtheria-tetanus-poliomyelitis-typhoid vaccination to induce modifications in protein metabolism was investigated in post-absorptive healthy humans. 2. Seven subjects were studied before and 2 days after vaccination. They underwent an intravenous primed constant infusion of L-[1-13C]leucine for 4h. Plasma protein concentrations, whole-body amino acid fluxes and acute-phase protein synthesis were determined. 3. Plasma concentrations of fibrinogen, alpha 1-acid glycoprotein, haptoglobin and alpha 1-antitrypsin were significantly elevated 2 days after vaccination (P < 0.05). Leucine oxidation was unaffected but whole-body protein synthesis and breakdown were both increased (P < 0.05), by 25 and 16% respectively, in subjects who had an elevated body temperature (n = 5). Albumin synthesis was unchanged, but hepatic synthesis of fibrinogen was 56% higher after vaccination. 4. The present investigation indicates that diphtheria-tetanus-poliomyelitis-typhoid vaccination could induce a sustained acute-phase reaction. Moreover, protein metabolism appeared to be extremely sensitive to a mild stress since leucine kinetics and fibrinogen synthesis were affected. Therefore, diphtheria-tetanus-poliomyelitis-typhoid vaccination might represent an attractive model for studying the inflammatory process in humans.

Vers une vaccination contre le paludisme

For 20 years, the prospect of anti-malarial vaccination has aroused many hopes, but in the end, it has mostly given rise to doubts and disappointment. If most attempts have been to no avail, this is because the issue at stake is amazingly difficult. Besides the very complex antigenic structure of the protozoa Plasmodium, there is first the existence of at least three different targets during the plasmodial cycle, then the necessity of appropriate adjuvants and, most of all, the imperfection of our experimental models. Recently, Pattaroyo and the various groups who worked with him have eventually met success with vaccine trials in man: they used a synthetic antigene, SPf66, on volunteers in South America, then on a larger population sample in East Africa. The results are still quite modest: people are protected against the malarial disease but not against the parasitemia and only in approximately 40% of cases. Nevertheless, these results have the merit of representing the first successful anti-malarial vaccination in man. Although great advances are still needed, a decisive step forward has been taken. Other types of vaccine will soon be tested by other groups (anti-gametocyte vaccines) and prospects of significant improvements are offered by the technique of DNA-vaccines. If it is now certain that one or several vaccines will be available in a near future, no one is able to set the time delay necessary to reach this stage. In any case, hoping that this type of vaccine will eradicate the disease is not realistic since a disease as complex as malaria, in terms of epidemiology, cannot be eliminated by only one method.(ABSTRACT TRUNCATED AT 250 WORDS)

The immune response to the blood stages of Plasmodium in animal models

Several models can be used to study the erythrocytic stages of Plasmodium in the vertebrate host. Although no single-model system reflects the human infection exactly, different systems taken together provide important information on the antigens necessary to stimulate protective immunity and the mechanisms of immunity and immunopathogenesis. Investigations, particularly in rodent models, have demonstrated the importance of CD4 + T cells in protective immunity to erythrocytic parasites and have shown that effector functions (Th1 and Th2) of these cells may play a role in parasite clearance. Because of the nature of the peptide—MHC interaction, animal models may not supply detailed information on the fine specificity of T-cell responses. However, immunisations of rodents and primates with a variety of recombinant proteins of Plasmodium will indicate the feasibility and limitations of using peptide vaccines in man.

Long-Term Humoral and Cellular Immunity after Vaccination with Cell Culture Rabies Vaccines in Man

To determine the duration of anti-rabies immunity, peripheral blood of 18 vaccinees was obtained between 2 and 14 years after immunization. Peripheral blood mononuclear cells (PBMC) and serum were tested for the presence of either rabies virus-specific antibodies or rabies antigenspecific proliferation. Neutralizing immunoglobulin class G anti-rabies virus antibodies could be detected in sera of all vaccinees, but not in 18 age- and sex-matched controls. Rabies antigen-induced proliferation of PBMCs from vaccinees was significantly higher than that of controls. The antirabies T and B cell response showed no time-dependent pattern. These results suggest the induction of a long-term immunity after rabies immunization according to pre- and postexposure schedules with inactivated cell culture vaccines against rabies.

Novel Adjuvant Strategies for Experimental Malaria and AIDS Vaccines

Adjuvant research has improved the ability of biotechnology to generate novel vaccines. Numerous strategies for enhancing the immunogenicity of synthetic peptides and proteins have been identified. This overview focuses on adjuvant development and vaccine delivery systems that provide new tools for amplifying the effectiveness of ongoing malaria and AIDS vaccine development programs. In addition, some of the complex challenges and issues that have become associated with the delivery of modern vaccines in man are outlined. As adjuvant research continues to open new opportunities in vaccine development, there is renewed expectation that further generations of safe and potent vaccines will be possible against a broad spectrum of infectious agents and cancer.

Efficacy trial of a parenteral gonococcal pilus vaccine in men

A randomized, placebo-controlled, double-blind efficacy trial of a purified gonococcal pilus vaccine composed of a single pilus type was tested in 3123 men and 127 women volunteers. Either 100 μg of vaccine or a placebo was given intradermally on day 1 and day 14. Each group was evenly matched with respect to age, sex, prior history of a sexually transmitted disease, sexual exposure during the study and attrition from the study. None of the women volunteers acquired gonorrhoea during the trial. In the male volunteers, 108 vaccine and 102 placebo recipients acquired gonorrhoea 15 days or later after the initial immunization. Vaccines developed a sustained ELISA antibody response to homologous and heterologous pili, but the latter titres were approximately 40% as high as the homologous pilus antibody rises. There were, however, no increases in inhibition of attachment antibody (IEA) titres. Local antibodies (semen) against homologous and heterologous strains were also elicited (ELISA). The vaccine was safe and did not alter the clinical expression of disease. This gonococcal pilus vaccine composed of a single pilus type failed to protect men against gonococcal urethritis.

The modulation of the specific and non-specific host response in case of influenza virus infection and vaccination in man

The modulation of the specific and non-specific host response in case of influenza virus infection and vaccination in man

Hepatitis B vaccination of haemodialysis patients: randomized controlled trial comparing plasma‐derived vaccine with and without pre‐S2 antigen

Abstract. The pre‐S2 protein of the hepatitis B virus envelope evokes anti‐pre‐S2 antibodies and enhances the anti‐HBs response after vaccination in mice. In order to evaluate the immunogenicity of the pre‐S2 Ag in man, 102 HBsAg, anti‐HBs, anti‐HBc‐negative haemodialysis patients were vaccinated at random according to one of four vaccination schedules: 5 μg plasma vaccine Pasteur (containing 1 % pre‐S2) or 20 μg plasma vaccine MSD (no pre‐S2) at 0, 1, 2, 4, 6 and 12 months; or 10 μg Pasteur or 40 μg MSD at 0, 1,2 and 6 months. Anti‐HBs levels were measured by RIA and expressed in IU 1‐1; anti‐pre‐S2 response was evaluated by both EIA and Western blot analysis.Eighty‐four per cent (95% confidence interval: 75–93) of the patients exhibited an anti‐HBs response of 2 IU l‐1 or more and 71% (95% confidence interval: 61–81) reached an anti‐HBs level of at least 10 IU l‐1 within 13 months of the start of vaccination. Anti‐HBs response correlated with age (the response rate decreased with increasing age) but not with either the type of vaccine or dosage. An anti‐pre‐S2 response was observed in 16% (EIA) and 46% (Western blot) of the patients immunized with the Pasteur vaccine and none (EIA, Western blot) of the MSD group. The level of anti‐pre‐S2 antibodies correlated with high anti‐HBs titres; an anti‐pre‐S2 response occurred in only one anti‐HBs‐negative patient.The addition of 1% pre‐S2 to the HBsAg plasma hepatitis B vaccine had no significant effect on the anti‐HBs response in haemodialysis patients and did not markedly broaden protective immunity. Further studies of recombinant vaccines with a higher pre‐S2 content are needed to document the possibility of enhanced immunogenicity of pre‐S2Ag‐containing hepatitis B vaccines in man.

In vitro induction of antigen specific antibody synthesis and proliferation of T lymphocytes with acellular pertussis vaccines, pertussis toxin and filamentous haemagglutinin in humans

The in vitro response of human B- and T-lymphocytes to the acellular vaccines JNIH-6 (containing pertussis toxoid and filamentous hemagglutinin), and JNIH-7 (containing pertussis toxoid), and to the purified components JNIH-4 (filamentous hemagglutinin) and JNIH-5 (pertussis toxin) was investigated. Pertussis toxoid and filamentous hemagglutinin induced specific Ig synthesis in vitro in lymphocytes obtained from convalescent pertussis patients as target cells. The antigen-dependent Ig production was demonstrated in lymphocyte culture supernatants by ELISA techniques and by a Chinese hamster ovary cell toxin neutralization assay. Particularly with JNIH-4, -6 and -7, high antibody titers were obtained. At optimal antigen concentrations a marked lymphocyte blast transformation was found in lymphocyte cultures from whooping cough patients, but not in cultures of lymphocytes obtained from healthy volunteers. At high concentrations native pertussis toxin as well as the B oligomer (S2–5) of the toxin induced a strong proliferation of patient as well as control lymphocytes, indicating non-specific mitogenic activity. At lower concentrations lymphocyte blast transformation was seen in patient cultures only, which indicates an antigen-specific T-cell response. The A protomer (S1), dimer 1(S2 + 4) and dimer 2(S3 + 4) induced proliferation of patient lymphocytes, which demonstrates the presence of T-cell epitopes on these peptides. The in vitro B-cell response and the lymphocyte blast transformation assay are both useful tools for estimating the potency of acellular pertussis vaccines in man. Spontaneously acquired and vaccine induced immunity to Bordetella pertussis can be investigated at the level of B- and T-lymphocytes.

Reactogenicity and immunogenicity of the newly developed Purified Chick Embryo Cell (PCEC)-rabies vaccine in man

Purified Chick Embryo Cell (PCEC) rabies vaccine was given to 88 healthy adults according to six different vaccination schedules. Local side effects were reported on reactivity forms after 16.4% of PCECV injections, general symptoms were recorded after 15.1% of the 292 doses administered. IgE antibodies specific for chicken proteins determined by the Radio Allergo Sorbens Test (RAST) could not be shown before and after the vaccinations. With no exception, all 88 vaccinees developed high titres of complement-fixing and neutralizing antibodies as determined by the Rapid Fluorescent Focus Inhibition Test and Serum Mouse Neutralization Test. For the first time, induction of serum interferon by PCEC rabies vaccine has been shown in man. In rabies vaccination, PCEC vaccine seems to be as effective as Human Diploid Cell Strain (HDCS) vaccine.

Host immune response and pathological expression in malaria: possible implications for malaria vaccines

Recent progress in parasite immunobiology has led to the identification of several plasmodial antigens representing the target of the protective antibody response of the infected host. As a consequence, some of these antigens have been envisaged as potential malaria vaccines in man. However, in spite of these achievements, the fine mechanisms which lead to the development of a state of partial protective immunity or to the triggering of immunopathology during malaria infection are not yet fully understood. Thus, it may be appropriate to evaluate the relative importance of individual host immune responsiveness to parasite epitopes involved in the induction of immunity, or of some immunologically mediated adverse reactions such as glomerulonephritis, anaemia, thrombocytopenia, and cerebral syndrome.