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Clin Infect Dis 2002 Mar 15;34(6):813-21
US Naval Medical Center, San Diego, CA, USA.
[Medline record in process]
We determined the immunogenicity and safety of reimmunization with the 23-valent polysaccharide pneumococcal vaccine in patients infected with human immunodeficiency virus type 1 (HIV-1). Patients immunized >5 years earlier (initially within 1 year of HIV-1 seroconversion) were randomized to receive vaccine (n=57) or placebo (n=30). Persons with recent HIV-1 seroconversion (n=14) were immunized for the first time. Preimmunization levels of capsule-specific immunoglobulin G were similar in all groups. Reimmunized patients showed a significantly lower frequency and magnitude of antibody responses compared with persons with recent HIV-1 seroconversion. Reimmunized patients did not show adverse virologic or immunologic changes, but some reported local discomfort (15%) or fever (8%). Thus, the limited responses after reimmunization of HIV-1-infected patients with the current 23-valent vaccine mandates the need for a more effective reimmunization schedule, more immunogenic vaccines, or other behavioral and therapeutic interventions.
PMID: 11850863, UI: 21838519
Clin Infect Dis 2002 Jan 1;34(1):84-90
Department of Medicine and Infection Prevention and Control Program, National Guard Health Affairs, King Fahad National Guard Hospital, Riyadh, Saudi Arabia. Memish@ngha.med.sa
Invasive meningococcal disease, in both endemic and epidemic forms, is the cause of significant morbidity and mortality worldwide. Despite all advances in therapy, the fatality rate of meningococcal meningitis remains unacceptably high, between 5% and 10%, and a similar proportion suffers long-term neurological sequalae. Prevention of this rapidly fatal disease is of paramount importance. The use of the available internationally licensed meningococcal vaccines would be indicated for individuals with medical conditions that increase the risk of the disease and for travelers to high-risk countries. In the last 2 years, there has been a shift in the epidemic pattern of meningococcal disease during the Hajj (pilgrimage) season, with predominance of Neisseria meningitidis serogroup W135. Recent changes have been made in the policy issued by the Saudi Ministry of Health (Riyadh, Saudi Arabia), which requires visitors from all over the world arriving for purposes of umra and Hajj to show evidence of vaccination against meningitis with the quadrivalent meningococcal vaccine.
PMID: 11731951, UI: 21587802
Clin Infect Dis 2002 Jan 1;34(1):79-83
The Johns Hopkins Center for Civilian Biodefense Studies, Baltimore, MD, USA. dahzero@aol.com
After eradication, there is a small but finite risk that smallpox and/or poliomyelitis viruses could accidentally escape from a laboratory or be released intentionally. The reintroduction of either virus into a highly susceptible population could develop into a serious catastrophe. To counter such an occurrence will require the use of vaccine, perhaps in substantial quantities. In the United States, new stocks of smallpox vaccine are being procured and arrangements are being made for a standby production facility. Similar provisions need to be considered for polio. To counter an epidemic of polio will require the use of the oral vaccine, which is presently the World Health Organization-recommended vaccine of choice for countries throughout the developing world. In these countries, its continued use is advised because of its ability to induce intestinal immunity, its ability to spread to other susceptible household members and to protect them, its ease of administration, and its low cost.
PMID: 11731949, UI: 21587800
Clin Infect Dis 2002 Jan 1;34(1):72-7
The polio eradication initiative, created after the World Health Assembly resolved, in 1988, to eradicate poliomyelitis globally by 2000, has made remarkable progress. From 1988 through 2000, the number of countries where polio was endemic decreased from >125 to 20, and the estimated number of polio cases decreased from 350,000 to <3500, for a percentage decrease of >99%. Wild-type 2 poliovirus has not been detected worldwide since October 1999, despite improving surveillance. The major focus of the eradication effort is to complete the task of stopping wild-type poliovirus transmission. Given the rapid progress made toward this goal, planning for the posteradication era has begun in earnest (1) to minimize the risk of reintroduction of virus into the population from laboratory stocks or long-term carriers, and (2) to prevent vaccine-derived polioviruses from circulating and causing outbreaks. This report summarizes the current thinking about these "endgame" issues, as put forth by the World Health Organization's technical advisory body for the initiative, the Technical Consultative Group on the Global Eradication of Poliomyelitis.
PMID: 11731948, UI: 21587799
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Infect Immun 2002 Mar;70(3):1566-70
Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine. Department of International Health, Johns Hopkins University Bloombers School of Public Health, Baltimore, Maryland 21205.
Mycobacterium microti is phylogenetically closely related to Mycobacterium tuberculosis and is a member of that complex of organisms. It is a curved, acid-fast bacillus that is naturally attenuated with a narrow host range for Microtus species only. In this study, we confirm the unique susceptibility of voles to infection with M. microti and the relative resistance of mice with a significantly lower organism burden after 8 weeks of infection. In addition, histopathologic examination of lungs reveals a lack of cellular, granulomatous aggregates characteristically seen in murine M. tuberculosis infection. In the past, M. microti has been used successfully in humans as a vaccine against tuberculosis but was associated with cutaneous reactions. In an attempt to circumvent this adverse effect, we report the efficacy of aerosol and oral vaccination with M. microti. High-dose orogastric vaccination with M. microti resulted in a statistically significant improvement in protection against aerosol challenge with virulent M. tuberculosis in the murine model compared with subcutaneous M. bovis BCG Pasteur vaccination.
PMID: 11854245, UI: 21843150
Infect Immun 2002 Mar;70(3):1507-17
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. gpriebe@rics.bwh.harvard.edu
Antibodies to the lipopolysaccharide O antigen of Pseudomonas aeruginosa mediate high-level immunity, but protective epitopes have proven to be poorly immunogenic, while nonprotective or minimally protective O-antigen epitopes often elicit the best immune responses. With the goal of developing a broadly protective P. aeruginosa vaccine, we used a gene replacement system based on the Flp recombinase to construct an unmarked aroA deletion mutant of the P. aeruginosa serogroup O2/O5 strain PAO1. The resultant aroA deletion mutant of PAO1 is designated PAO1 Delta aroA. The aroA deletion was confirmed by both PCR and failure of the mutant to grow on minimal media lacking aromatic amino acids. When evaluated for safety and immunogenicity in mice, PAO1 Delta aroA could be applied either intranasally or intraperitoneally at doses up to 5 x 10(9) CFU per mouse without adverse effects. No dissemination of PAO1 Delta aroA to blood, liver, or spleen was detected after intranasal application, and histological evidence of pneumonia was minimal. Intranasal immunization of mice and rabbits elicited high titers of immunoglobulin G to whole bacterial cells and to heat-stable bacterial antigens of all seven prototypic P. aeruginosa serogroup O2/O5 strains. The mouse antisera mediated potent phagocytic killing of most of the prototypic serogroup O2/O5 strains, while the rabbit antisera mediated phagocytic killing of several serogroup-heterologous strains in addition to killing all O2/O5 strains. This live, attenuated P. aeruginosa strain PAO1 Delta aroA appears to be safe for potential use as an intranasal vaccine and elicits high titers of opsonic antibodies against multiple strains of the P. aeruginosa O2/O5 serogroup.
PMID: 11854239, UI: 21843144
Infect Immun 2002 Mar;70(3):1443-52
Department of Immunology, Landspitali-University Hospital, Reykjavik, Iceland.
Immunization with pneumococcal polysaccharides (PPS) conjugated to tetanus toxoid (TT) (Pnc-TT) elicits protective immunity in an adult murine pneumococcal infection model. To assess immunogenicity and protective immunity in early life, neonatal (1 week old) and infant (3 weeks old) mice were immunized intranasally (i.n.) or subcutaneously (s.c.) with Pnc-TT of serotype 1 (Pnc1-TT). Anti-PPS-1 and anti-TT immunoglobulin G (IgG) and IgM antibodies were measured in serum and saliva, and vaccine-induced protection was evaluated by i.n. challenge with serotype 1 pneumococci. Pnc1-TT was immunogenic in neonatal and infant mice when administered s.c. without adjuvant: a majority of the young mice were protected from bacteremia and a reduction of pneumococcal density in the lungs was observed, although antibody responses and protective efficacy remained lower than in adults. The addition of LT-K63, a nontoxic mutant of heat-labile enterotoxin, as adjuvant significantly enhanced PPS-1-specific IgG responses and protective efficacy following either s.c. or i.n. Pnc1-TT immunization. Mucosal immunization was particularly efficient in neonates, as a single i.n. dose of Pnc1-TT and LT-K63 induced significantly higher PPS-1-specific IgG responses than s.c. immunization and was sufficient to protect neonatal mice against pneumococcal infections, whereas two s.c. doses were required to induce complete protection. In addition, i.n. immunization with Pnc1-TT and LT-K63 induced a vigorous salivary IgA response. This suggests that mucosal immunization with pneumococcal conjugate vaccines and LT-K63 may be able to circumvent some of the limitations of neonatal antibody responses, which are required for protective immunity in early life.
PMID: 11854231, UI: 21843136
Infect Immun 2002 Mar;70(3):1434-42
Department of Pharmacy, Biomedical Center, Uppsala University, SE-751 23 Uppsala SBL Vaccin AB, SE-105 21 Stockholm, Sweden.
We have studied polyacryl starch microparticles as an adjuvant in oral vaccination in mice. Secreted antigens from Salmonella enterica serovar Enteritidis were administered covalently conjugated to microparticles, or as free antigens, orally or intramuscularly and evaluated for their immunogenicity and ability to elicit protective immune response against an oral challenge with live serovar Enteritidis. The highest immunoglobulin M (IgM)-plus-IgG titers were obtained in the groups immunized with antigen-conjugated microparticles. The subclass profile switched to a stronger Th1 influence in the oral groups after booster, while the intramuscular group showed a constant Th1/Th2 profile. A strong specific IgA response was seen in feces in the oral groups, which was further confirmed in an enzyme-linked immunospot assay. The delayed-type hypersensitivity test, as a measure of the cellular response, showed a significant increase in ear thickness in all the immunized groups, except for the group that received free antigen orally, compared to the nonimmunized group. The cytokines released from in vitro-stimulated spleens showed a strong gamma interferon response in all immunized groups. A significant reduction in CFU in liver and spleen was seen in the orally immunized groups compared to the nonimmunized group after oral challenge with serovar Enteritidis. Western blotting analysis with both sera and feces revealed that antibodies against three bands, 53, 56, and 60 kDa, dominated the oral groups, and an electrospray-mass spectroscopy analysis of these bands showed amino acid sequences coinciding with those of phase-1 flagellin and hook-associated protein 2.
PMID: 11854230, UI: 21843135
Infect Immun 2002 Mar;70(3):1417-21
Molecular Immunology Group, Nuffield Department of Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom. elee@enterprise.molbiol.ox.ac.uk
Plasmodium falciparum malaria is a major cause of death in the tropics. The 19-kDa subunit of P. falciparum merozoite surface protein 1 (MSP-1(19)), a major blood stage vaccine candidate, is the target of cellular and humoral immune responses in animals and humans. In this phase I trial of MSP-1(19), immunization of nonexposed human volunteers with either of the two allelic forms of recombinant MSP-1(19) induced high levels of antigen-specific Th1 (gamma interferon) and Th2 (interleukin 4 [IL-4] and IL-10) type lymphokines. The adjustment of the antigen dose and number of immunizations regulated the level of specificity of immune responses and Th1/Th2 bias of responses induced by vaccination. Novel conserved and allelic T-cell epitopes which induced cross-strain immune responses were identified. Importantly, responses to many of these novel epitopes were also present in adults exposed to malaria, both in east (Kenya) and west Africa (The Gambia). These data suggest that epitope-specific naturally acquired MSP-1(19) immune responses in endemic populations can be boosted by vaccination.
PMID: 11854228, UI: 21843133
Infect Immun 2002 Mar;70(3):1245-53
Department of Medical Microbiology and Immunology, Texas A&M University System Health Science Center, College Station, Texas 77843-1114, USA. ajeevan@medicine.tamu.edu
The effect of Mycobacterium bovis BCG vaccination on interleukin-1 beta (IL-1 beta) or regulated-upon-activation, normally T-cell-expressed and -secreted chemokine (RANTES) mRNA expression in guinea pig spleen cells stimulated with concanavalin A, lipopolysaccharide (LPS), phorbol myristate acetate (PMA) plus ionomycin, or purified protein derivative (PPD) was studied in vitro. Similarly, peritoneal exudate cell-derived macrophages from naive and BCG-vaccinated guinea pigs were infected with M. bovis BCG, Mycobacterium avium, the attenuated Mycobacterium tuberculosis H37Ra strain, or virulent strains H37Rv and Erdman of M. tuberculosis. Total RNA was subjected to Northern blot analysis using probes generated from guinea pig IL-1 beta or RANTES cDNA. Although IL-1 beta and RANTES mRNA could be detected in the spleen cells from naive animals stimulated with LPS or PMA plus ionomycin, the levels were significantly enhanced after BCG vaccination. mRNA expression was also elevated in macrophages infected with live mycobacteria after BCG vaccination. However, macrophages infected with the virulent H37Rv strain of M. tuberculosis showed 75 to 90% reductions in IL-1 beta expression and 25 to 60% reductions in RANTES mRNA expression compared with macrophages infected with the attenuated H37Ra strain. The IL-1 beta mRNA levels peaked as soon as 1 h after PPD stimulation and 4 h after M. tuberculosis H37Rv infection of macrophages. In contrast, RANTES mRNA expression was delayed until 48 h after infection. These results indicate that molecular mediators produced in response to various stimuli associated with protective immunity against mycobacteria are upregulated after BCG vaccination; however, a significantly weaker response was observed with virulent M. tuberculosis. These initial studies indicate that BCG vaccination has a positive effect on IL-1 beta and RANTES mRNA expression by host cells in a highly relevant animal tuberculosis model.
PMID: 11854207, UI: 21843112
Infect Immun 2002 Feb;70(2):679-84
Division of Bacteriology, National Institute for Biological Standards and Control, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, United Kingdom.
The mechanism whereby whole-cell pertussis vaccines (WCV) confer protection against Bordetella pertussis is still not fully understood. We have previously reported that macrophage activation produced by vaccination with WCV is associated with induction of NO synthesis by macrophages in response to in vitro stimulation with B. pertussis antigens. To determine whether NO production is an effector of protection or simply a marker of activation, the susceptibility of inducible nitric oxide synthase (type II, iNOS) knockout mice to infection with B. pertussis was examined. We showed that iNOS knockout mice were more susceptible to B. pertussis respiratory challenge than wild-type mice. iNOS-deficient mice also developed a less effective protective response than wild-type mice after the same immunization with WCV. This suggests that NO plays an important role in effecting protection against B. pertussis challenge.
PMID: 11796599, UI: 21655154
Infect Immun 2002 Feb;70(2):544-60
Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona 74100, Israel.
The efficacy of passive immunization as a postexposure prophylactic measure for treatment of guinea pigs intranasally infected with Bacillus anthracis spores was evaluated. Antisera directed either against the lethal toxin components (PA or LF) or against a toxinogenic strain (Sterne) were used for this evaluation. All antisera exhibited high enzyme-linked immunosorbent assay titers against the corresponding antigens, high titers of neutralization of cytotoxicity activity in an in vitro mouse macrophages cell line (J774A.1), as well as in vivo neutralization of toxicity when administered either directly to Fisher rats prior to challenge with the lethal toxin or after incubation with the lethal toxin. In these tests, anti-LF antiserum exhibited the highest neutralization efficiency, followed by anti-Sterne and anti-PA. The time dependence and antibody dose necessary for conferring postexposure protection by the various antibodies of guinea pigs infected with 25 50% lethal doses of Vollum spores was examined. Rabbit anti-PA serum was found to be the most effective. Intraperitoneal injections of anti-PA serum given 24 h postinfection protected 90% of the infected animals, whereas anti-Sterne and anti-LF were less effective. These results further emphasizes the importance of anti-PA antibodies in conferring protection against B. anthracis infection and demonstrated the ability of such antibodies to be effectively applied as an efficient postexposure treatment against anthrax disease.
PMID: 11796581, UI: 21655136
J Immunol 2002 Mar 1;168(5):2523-2529
Center of Molecular Immunology and National Institute of Oncology and Radiobiology, Havana, Cuba. ELEA Laboratories, Buenos Aires, Argentina.
[Record supplied by publisher]
We generated the 1E10 gamma-type anti-idiotype mAb (Ab2) specific to an Ab1 mAb able to react specifically with N-glycolyl-containing gangliosides and with Ags expressed on human melanoma and breast carcinoma cells. This Ab2 mAb induced an Ab response in animal models sharing immunochemically defined idiotopes with the Ab1. The treatment of tumor-bearing mice with 1E10 mAb induced a strong antitumor activity. A clinical trial was conducted in 20 patients with advanced malignant melanoma. Patients were treated with six intradermal injections of aluminum hydroxide-precipitated 1E10 anti-Id mAb given at 2-wk intervals. Sixteen of the 17 patients who received at least four doses of the anti-Id vaccine develop Ab3 Abs capable of inhibiting Ab2 binding to Ab1 (Ab3Id+). In contrast to the incapacity of 1E10 mAb to generate Ab3 Abs with the same antigenic specificity as the Ab1 mAb in mice, a very specific and strong Ab3 response against N-glycolyl-containing gangliosides was induced in 16 patients (Ab3Ag+). No evidence of serious or unexpected adverse effects has been observed in this clinical trial. 1E10 anti-Id vaccine was safe, well tolerated, and immunologically effective, with most patients being able to generate a specific immune response against 1E10 and Neu-glycolyl-GM(3) ganglioside.
PMID: 11859147
J Virol 2002 Feb;76(4):1649-62
Department of Microbiology, Hannam University, Daejeon. Creagene Research Institute, Department of Genetic Engineering, Youngdong University, Youngdong. Korea Research Institute of Bioscience and Bioengineering, Daejeon South Korea.
Poliovirus has been studied as a live recombinant vaccine vector because of its attractive characteristics. The genetic instability, however, has hampered recombinant polioviruses (PVs) from being developed as an appropriate vaccine. A variety of different foreign inserts were cloned directly into our poliovirus Sabin 1-based RPS-Vax vector system, resulting in the production of recombinant PVs. The genetic stability of each recombinant PV was examined during 12 rounds of consecutive passage. It was found that the genetic stability of the recombinants was not well correlated with their insert size. Instead, elevated stability was frequently observed in recombinants with inserts of high G/C contents. Furthermore, a comparative study using different constructs of the human immunodeficiency virus env gene revealed that the internal deletion of the unstable insert was seemingly caused by the presence of the adjacent A/T-rich region. The instability of these inserts was completely remedied by (i) increasing the G/C contents and (ii) replacing the local A/T-rich region with the G/C-rich codon without a change of the amino acid. This means that stability is closely associated with the G/C content and the G/C distribution pattern. To see whether these findings can be applied to the design of genetically stable recombinant PV, we have reconstructed the heteromultimeric insert based on our design architecture, including the above-mentioned G/C rules and the template/ligation-free PCR protocol. The heteromultimeric insert was very unstable, as expected, but the manipulated insert with the same amino acid sequence showed complete genetic stability, not only in vitro, but also in vivo. Even though this guideline was established with our RPS-Vax vector system, to some extent, it can also be applied to other live viral vaccine vectors.
PMID: 11799160, UI: 21657440
JAMA 2002 Feb 13;287(6):702-3
PMID: 11851515, UI: 21841443
JAMA 2002 Feb 6;287(5):579
PMID: 11838446, UI: 21827077
JAMA 2002 Feb 6;287(5):575-6
Publication Types:
PMID: 11829676, UI: 21819132
N Engl J Med 2002 Feb 7;346(6):429-37
Division of Infectious Diseases, Children's Hospital, Boston, MA 02115, USA. kenneth.mcintosh@tch.harvard.edu
PMID: 11832532, UI: 21822563
Pediatrics 2002 Jan;109(1):172
PMID: 11773568, UI: 21635854
Science 2002 Feb 1;295(5556):777
PMID: 11823609, UI: 21681967
Science 2002 Jan 25;295(5555):598-9
PMID: 11809941, UI: 21669285
Vaccine 2002 Feb 22;20(11-12):1681-1691
United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, 21702-5011, Fort Detrick, MD, USA
Mucosal (oral) immunization of mice with carrier-delivered ricin toxoid (RT) vaccine was accomplished by one long (7 weeks) or two short (4 weeks) immunization schedules. For the long and short immunization schedule two lots of vaccine were administered prepared with the same procedure but at different occasions. The long schedule consisted of a total of seven doses of 50mug of vaccine in microencapsulated (lot #108) or aqueous form administered on days 1, 2, 3, 28, 29, 30 and 49. With the short schedule a total of seven or six doses of 25mug (lot #111) were administered on days 1, 2, 3, 14, 15, 16 and 30, or on 1, 2, 14, 15, 30, 31 and 32, respectively. Mice immunized orally with the long schedule, 50mug of RT vaccine incorporated into poly-DL-lactide-co-glycolyde (DL-PLG) microspheres (MS) produced serum IgG, IgG2a and IgA ELISA antibodies. All mice immunized with RT in DL-PLG MS (RT-MS) were protected against a lethal ricin aerosol challenge. In contrast, with the same schedule and with the same dose, the aqueous vaccine (RT) failed to stimulate IgG, IgG2a and IgA antibodies, and these mice were not protected against an aerosol ricin toxin challenge. With the shorter immunization scheme, seven doses of 25mug RT-MS stimulated a significant, though reduced, protection with the microencapsulated, but not with the aqueous vaccine. When the first and second 3-day cycles of the short immunization schedule was reduced to two doses, and the 3-day cycle was administered at the end of the schedule, neither RT-MS nor RT stimulated protection against the challenge. These results indicated that successful oral immunization with RT-MS depended on both the dose and the schedule, consisting of three consecutive days of administration in two cycles, 4 weeks apart. Altering this schedule and the dose, resulted in a reduced protection or no protection at all. Furthermore, under the conditions of this study, the advantage of the microencapsulated RT vaccine over the aqueous vaccine for effective oral immunization was well demonstrated.
PMID: 11858879
Vaccine 2002 Feb 22;20(11-12):1675-80
Malaria Program, Naval Medical Research Center, 503 Robert Grant Avenue, 20910, Silver Spring, MD, USA
Aotus lemurinus lemurinus monkeys were immunized four times with one of three DNA plasmids expressing important Plasmodium falciparum blood stage vaccine candidate proteins or with a mixture containing all three vaccines. The three vaccines encoded sequences from apical merozoite antigen-1 (AMA-1), erythrocyte binding protein-175 (EBA-175) and merozoite surface protein-1 (MSP-1). Antigen-specific enzyme-linked immunosorbant assays (ELISAs) showed no significant differences in antibody titer induced to the three antigens by a single vaccine compared with the titer induced to that same antigen by the trivalent preparation. Results of immunofluorescent antibody assays against erythrocytes infected with asexual blood stage P. falciparum indicated that each of the three monovalent vaccines induced significant antibody responses to whole parasites. The trivalent vaccine mixture induced, after four immunizations, an antibody titer to whole parasites that was 3-12-fold higher than those induced by any of the single vaccines. The fourth immunization with the trivalent vaccine increased the mean antibody in IFAT by more than five-fold.
PMID: 11858878, UI: 21848607
Vaccine 2002 Feb 22;20(11-12):1670-4
Department of Microbiology & Immunology, New York Medical College, 10595, Valhalla, NY, USA
Influenza viruses neuraminidase (NA) were chromatographically extracted from influenza viruses A/Nanchang/933/95 H3(NC)N2(NC) [R] and A/Johannesburg/82/96 H1(JH)N1(JH) [R] and used to supplement conventional inactivated trivalent influenza vaccine. Immunization of mice with this preparation resulted in high titers of antibodies to both hemagglutinins (HA) and neuraminidases (NA); there were no significant differences in the anti-HA antibody titers between the conventional and the supplemented vaccine preparation. Likewise, there were no significant differences in anti-NA antibody titers between the supplemented vaccine and titers from mice immunized with a neuraminidase vaccine containing a mixture of N1-NA and N2-NA. There was no evidence of a diminution of the immune response to the HA components of the vaccine despite the presence of antigenically equivalent amounts of both N1-NA and N2-NAs. Homotypic and distantly related heterotypic infections for both H1, N1 and H3N2 subtypes were suppressed and greater reduction in pulmonary virus titers (PVT) were observed in the trivalent vaccine supplemented with purified neuraminidase from each subtype, N1 and N2. Effects on the influenza B viral components were not studied. Previous studies on supplementation of conventional influenza vaccine focused only on monovalent H3N2 vaccine preparations; this study demonstrates in a mouse model system that supplementation of trivalent influenza vaccine with both influenza A subtype neuraminidases, N1 and N2 is highly immunogenic for HA and NA of each subtype and efficacious in protecting against influenza from homotypic and heterotypic infectious challenges of either subtype.
PMID: 11858877, UI: 21848606
Vaccine 2002 Feb 22;20(11-12):1649-52
Department of Medical Research (Lower Myanmar), Vaccine Production and Distribution Division, 5 Ziwaka Road, Dagon PO, 11191, Yangon, Myanmar
A total of 280 apparently healthy volunteers were screened for hepatitis B (HB) markers out of which 49 subjects (17.5%) were positive for HB surface antigen (HBsAg) and 82 (29.3%) were positive for antibody to HBsAg (anti-HBs). Three doses of DMR-HB vaccine, 0.15ml per dose were administered to 95 subjects, who were serologically negative for both HB markers. The vaccination was given by the intradermal route on the flexor surface of the left forearm, at 1 month intervals according to the 0, 1 and 2 months schedule. The subjects were carefully monitored to record any adverse reaction of the vaccine. Blood specimen was collected from each subject, 1 month after the second and third vaccinations, to determine the anti-HBs antibody response to the vaccine. The study results showed that local pain was the only side effect noted and protective antibodies (anti-HBs) were detected in 69 (72.6%) of the vaccinees after the second dose of the vaccine and 89 (93.6%) after the third dose of the vaccine. Thus the intradermal route, which would require approximately one-seventh of the standard dose, would be suitable for use in certain groups such as high risk adults, when the cost of the vaccine is the inhibiting factor for routine or mass vaccination.
PMID: 11858874, UI: 21848603
Vaccine 2002 Feb 22;20(11-12):1624-30
Merck Vaccine Division, Merck and Company, P.O. Box 4, WP97A-343, 19486-0004, West Point, PA, USA
Evidence based vaccinology (EBV) is the identification and use of the best evidence in making and implementing decisions during all of the stages of the life of a vaccine, including pre-licensure vaccine development and post-licensure manufacture and research, and utilization of the vaccine for disease control. Vaccines, unlike most pharmaceuticals, are in a continuous process of development both before and after licensure. Changes in biologics manufacturing technology and changes that vaccines induce in population and disease biology lead to periodic review of regimens (and sometimes dosage) based on changing immunologic data or public perceptions relevant to vaccine safety and effectiveness. EBV includes the use of evidence based medicine (EBM) both in clinical trials and in national disease containment programs. The rationale for EBV is that the highest evidentiary standards are required to maintain a rigorous scientific basis of vaccine quality control in manufacture and to ensure valid determination of vaccine efficacy, field effectiveness and safety profiles (including post-licensure safety monitoring), cost-benefit analyses, and risk:benefit ratios. EBV is increasingly based on statistically validated, clearly defined laboratory, manufacturing, clinical and epidemiological research methods and procedures, codified as good laboratory practices (GLP), good manufacturing practices (GMP), good clinical research practices (GCRP) and in clinical and public health practice (good vaccination practices, GVP). Implementation demands many data-driven decisions made by a spectrum of specialists pre- and post-licensure, and is essential to maintaining public confidence in vaccines.
PMID: 11858871, UI: 21848600
Vaccine 2002 Feb 22;20(11-12):1609-17
Bernard and Gloria Salick Equine Viral Disease Laboratory, Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, One Shields Ave., University of California, 95616, Davis, CA, USA
Replicon particles derived from a vaccine strain of Venezuelan equine encephalitis (VEE) virus were used as vectors for expression in vivo of the major envelope proteins (G(L) and M) of equine arteritis virus (EAV), both individually and in heterodimer form (G(L)/M). The immunogenicity of the different replicons was evaluated in horses, as was their ability to protectively immunize horses against intranasal and intrauterine challenge with a virulent strain of EAV (EAV KY84). Horses immunized with replicons that express both the G(L) and M proteins in heterodimer form developed neutralizing antibodies to EAV, shed little or no virus, and developed only mild or inapparent signs of equine viral arteritis (EVA) after challenge with EAV KY84. In contrast, unvaccinated horses and those immunized with replicons expressing individual EAV envelope proteins (M or G(L)) shed virus for 6-10 days in their nasal secretions and developed severe signs of EVA after challenge. These data confirm that replicons that co-express the G(L) and M envelope proteins effectively, induce EAV neutralizing antibodies and protective immunity in horses.
PMID: 11858869, UI: 21848598
Vaccine 2002 Feb 22;20(11-12):1603-1608
Centers for Disease Control and Prevention, Epidemic Intelligence Service, 30333, Atlanta, GA, USA
Context: The vaccine adverse event reporting system (VAERS) monitors vaccine safety post-licensure. Although events reported to VAERS are not necessarily causally associated with vaccination, VAERS reports can be used to identify possible safety concerns that occur at too low a rate to have been identified prior to licensure.Objective: To evaluate adverse events following Lyme disease vaccination reported to VAERS during the first 19 months of the vaccine's licensure.Design, setting, and participants: Analysis of all VAERS reports of adverse events following vaccination for Lyme disease in the US from 28 December 1998 to 31 July 2000.Main outcome measure: We evaluated reported adverse events for unexpected patterns in age, gender, time to onset, dose number, and clinical characteristics and compared them to adverse events observed in clinical trials of this vaccine.Results: Over 1,400,000 doses were distributed and 905 adverse events were reported to VAERS, 440 in men and 404 in women, with ages ranging from 10 to 82 years. The majority (56%) of adverse events occurred after administration of the first dose. The most frequently reported adverse events were arthralgia (250), myalgia (195), and pain (157). There were 59 reports coded as arthritis, 34 as arthrosis, 9 as rheumatoid arthritis, and 12 as facial paralysis. Sixty-six (7.4%) events were classified as serious, involving life-threatening illness, hospitalization, prolongation of hospitalization, persistent or significant disability/incapacity, or death. Twenty-two hypersensitivity reactions were reported.Conclusions: Based on reporting to VAERS, we did not detect unexpected or unusual patterns of reported adverse events following Lyme disease vaccine administration, other than hypersensitivity reactions, compared with adverse events observed in clinical trials.
PMID: 11858868
Vaccine 2002 Feb 22;20(11-12):1593-602
Department of Applied Genetics, Institut de Biologie et de Medecine Moleculaires, Universite Libre de Bruxelles, Rue des Professeurs Jeener et Brachet 12, B-6041, Gosselies, Belgium
The varicella-zoster virus (VZV) envelope glycoprotein E (gE) and immediate early protein 63 (IE63) are well known targets for specific humoral and cell-mediated immune responses during VZV infection and latency, respectively. The present study evaluated the immunogenicity of an engineered chimeric recombinant gE-IE63 (recgE-IE63) protein secreted from CHO cells, wherein a soluble form of gE, deleted of its anchor and cytoplasmic domains was fused to IE63. Guinea pig vaccinations with adjuvanted recgE-IE63 elicited a strong and specific humoral immune response directed to each counterpart. Sera from recgE-IE63-immunized animals neutralized cell-free VZV. This neutralizing capacity was dependent only on the recgE moiety as serum depletions on recgE-immobilized sepharose totally abolished VZV neutralization. The cell-mediated immune response induced by recgE-IE63 was evaluated in lymphoproliferation assays. An antigen-specific proliferative response was demonstrated after lymphocyte stimulation with recIE63 but not with recgE. We conclude that recombinant chimeric recgE-IE63 induced both humoral and cell-mediated immune responses and thus could constitute a putative subunit vaccine candidate against VZV primary infection and zoster reactivation.
PMID: 11858867, UI: 21848596
Vaccine 2002 Feb 22;20(11-12):1586-1592
Department of Microbiology & Immunology, Dalhousie University, NS, B3H 4H7, Halifax, Canada
The radiation-resistant bacterium, Deinococcus radiodurans contains a variety of phospho-, glyco- and phosphoglycolipids, the structures of which appear to be largely unique in nature. We show here that such lipids are immunogenic when administered as liposomes intranasally in mice, as evidenced by the induction of serum antibodies which recognize D. radiodurans lipids but not other lipids by thin layer chromatographic immunostaining. By modifying a liposomal vaccine against respiratory syncytial virus (RSV) we find that vaccine efficacy is markedly enhanced by the inclusion of lipids isolated from D. radiodurans. Using dioleoylphosphatidylcholine (DOPC) or D. radiodurans lipids, liposomes were prepared which encapsulated a soluble fragment of the RSV G protein (G(128--188)) fused with a portion of the bacterial thioredoxin (Trx) protein. Mice immunized intranasally with D. radiodurans liposomes showed markedly greater protection against RSV challenge over mice immunized with DOPC liposomes. Enhanced vaccine efficacy was achieved using liposomes prepared from either whole D. radiodurans lipids or from a single isolated phosphoglycolipid previously identified as alpha-galactosylphosphatidylglyceroylalkylamine (lipid 7). Mice immunized and protected against RSV challenge were free of pulmonary eosinophilic infiltration, an undesirable consequence of many RSV vaccines. The results provide further support for liposome-based vaccines for RSV and underline the importance of lipid composition in liposome formulations.
PMID: 11858866
Vaccine 2002 Feb 22;20(11-12):1557-1562
Department of Pediatrics, School of Medicine of Ribeirao Preto, University of Sao Paulo, Av. dos Bandeirantes no. 3900, Ribeirao Preto, Sao Paulo, Brazil
The immunogenicity of a Hepatitis B vaccine was evaluated in 110 neonates (57 full term and 53 preterm) born to Hepatitis B surface antigen (HBsAg) negative mothers. Three 10mug doses of recombinant Hepatitis B vaccine were administered: the first dose within the first week of life; the second between 1 and 2 months; and the third at 5--7 months of age. Anti-HBs antibody titres were measured 3 months after the third dose. The seroconversion rate in preterm infants (77%; 95% CI=64.7--87.1) was significantly lower than in full term infants (98%; 95% CI=91.6--99.9) while the mean anti-HBs titres among those infants that did seroconvert was lower in preterm (186.6mIUml(minus sign1)) than in full term infants (537.5mIUml(minus sign1)). More full term than preterm infants showed titres greater than 100mIUml(minus sign1) (71.9 and 41.5%, respectively). We conclude that the administration of a recombinant Hepatitis B vaccine shortly after birth is less immunogenic in preterm infants weighing <1800g at birth than in full term infants. Currently accepted recommendations for post exposure perinatal prophylaxis may be inadequate to protect preterm infants.
PMID: 11858862
Vaccine 2002 Feb 22;20(11-12):1544-56
Division of Infectious Diseases and Food Chain Quality, Institute for Animal Science and Health (ID-Lelystad), P.O. Box 65, 8200 AB, Lelystad, The Netherlands
Three mutants with deletions in the E2 gene of the infectious DNA copy of the classical swine fever virus (CSFV) strain-C were constructed: one missing the B/C domain of CSFV-E2 between amino acids (aa) 693 and 746, one missing the A domain between aa 800 and 864, and one missing the complete E2 between aa 689 and 1062. All three CSFV-E2 deletion mutants were unable to generate viable virus, indicating that each of the antigenic domains of E2 is essential for viability of CSFV. To rescue the CSFV-E2 deletion mutants SK6 cell lines constitutively expressing glycoprotein E2 of CSFV were generated. The rescued viruses infected and replicated in SK6 cells as demonstrated by expression of viral proteins, but this primary infection did not result in reproduction of infectious virus. Thus, these E2 complemented viruses are considered non-transmissible. In previous experiments, we showed that simultaneous injection of E(rns) complemented virus (Flc23) via intradermal (ID), intramuscular (IM) or intranasal (IN) routes conferred protection to pigs against a lethal challenge with CSFV [J. Virol. 74 (2000) 2973]. Here, we evaluate different routes of application (ID, IM or IN) with E(rns) complemented virus Flc23 in order to find the best route for complemented CSFVs. Intradermal injection with Flc23 protected pigs against a lethal CSFV challenge, whereas intramuscular injection induced partial protection, and intranasal injection did not mediate a protective immune response in pigs at all. We used the intradermal route of vaccination to test the E2 complemented viruses. Vaccination of pigs via the intradermal route with the E2 complemented CSFVs also resulted in the induction of antibodies and in (partial) protection against CSFV challenge. Pigs vaccinated with E2 complemented virus Flc4 (deletion B/C domain) survived a lethal CSFV challenge, whereas partial protection was induced in pigs vaccinated with Flc47 (deletion E2) or Flc48 (deletion A domain) E2 complemented viruses. Serological data demonstrate that these E2 complemented mutant viruses are, in combination with well known diagnostic tests based on E2, potential marker vaccines for CSF.
PMID: 11858861, UI: 21848590
