Pre-clinical toxicity & immunobiological evaluation of DNA rabies vaccine & combination rabies vaccine in rhesus monkeys (Macaca mulatta)

Background & objectives: Pre-clinical toxicology evaluation of biotechnology products is a challenge to the toxicologist. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed recombinant DNA anti-rabies vaccine DRV (100 mu g)] and combination rabies vaccine CRV (100 mu g DRV and 1.25 IU of cell culture-derived inactivated rabies virus vaccine)], which are intended for clinical use by intramuscular route in Rhesus monkeys. Methods: As per the regulatory requirements, the study was designed for acute (single dose - 14 days), sub-chronic (repeat dose - 28 days) and chronic (intended clinical dose - 120 days) toxicity tests using three dose levels, viz. therapeutic, average (2x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in monkeys. The selection of the model i.e. monkey was based on affinity and rapid higher antibody response during the efficacy studies. An attempt was made to evaluate all parameters which included physical, physiological, clinical, haematological and histopathological profiles of all target organs, as well as Tiers I, II, III immunotoxicity parameters. Results: In acute toxicity there was no mortality in spite of exposing the monkeys to 10XDRV. In sub chronic and chronic toxicity studies there were no abnormalities in physical, physiological, neurological, clinical parameters, after administration of test compound in intended and 10 times of clinical dosage schedule of DRV and CRV under the experimental conditions. Clinical chemistry, haematology, organ weights and histopathology studies were essentially unremarkable except the presence of residual DNA in femtogram level at site of injection in animal which received 10X DRV in chronic toxicity study. No Observational Adverse Effects Level (NOAEL) of DRV is 1000 ug/dose (10 times of therapeutic dose) if administered on 0, 4, 7, 14, 28th day. Interpretation & conclusions: The information generated by this study not only draws attention to the need for national and international regulatory agencies in formulating guidelines for pre-clinical safety evaluation of biotech products but also facilitates the development of biopharmaceuticals as safe potential therapeutic agents.

Vaccination for pregnant women: Need to address

Pregnancy is a critically important state for any women in her life time. Administration of a vaccine to a pregnant woman is not a routine event and it is generally preferred to administer vaccines either prior to conception or in the postpartum period. Currently vaccination with inactivated vaccines are recommended due to potential risk to mother and fetus with live vaccines. Multiple factors determine the administration of the vaccines for example age, life style, medical conditions (e.g., asthma, diabetes etc.), type and location of travel and status of previous vaccination. If pregnant woman is exposed to these vaccines or if pregnancy occurs soon after vaccination, the women should be counselled regarding the risks to the fetus and vaccination should not be a reason to consider termination of pregnancy. Further research in vaccination among pregnancy is warranted for the safety of the pregnant women and their newborn for a healthy living and better life.

Stalking influenza by vaccination with pre-fusion headless HA mini-stem

Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.

An observer-based vaccination control law for an SEIR epidemic model based on feedback linearization techniques for nonlinear systems

This paper presents a vaccination strategy for fighting against the propagation of epidemic diseases. The disease propagation is described by an SEIR (susceptible plus infected plus infectious plus removed populations) epidemic model. The model takes into account the total population amounts as a refrain for the illness transmission since its increase makes the contacts among susceptible and infected more difficult. The vaccination strategy is based on a continuous-time nonlinear control law synthesised via an exact feedback input-output linearization approach. An observer is incorporated into the control scheme to provide online estimates for the susceptible and infected populations in the case when their values are not available from online measurement but they are necessary to implement the control law. The vaccination control is generated based on the information provided by the observer. The control objective is to asymptotically eradicate the infection from the population so that the removed-by-immunity population asymptotically tracks the whole one without precise knowledge of the partial populations. The model positivity, the eradication of the infection under feedback vaccination laws and the stability properties as well as the asymptotic convergence of the estimation errors to zero as time tends to infinity are investigated.

On some new mathematical models for infective diseases: analysis, equilibrium, positivity and vaccination controls

196 p.

Humoral and protective response of Indian major carps to immersion vaccination with Aeromonas hydrophila

Fry of the Indian major carps, Catta catla (Ham.), Labeo rohita (Ham.) and Cirrhinus mrigala (Ham.) were immunized at 4 and 8 weeks post hatching (wph) by direct immersion in a suspension (10 super(8) cells ml super(-1))of heat inactivated Aeromonas hydrophila. Following the same procedure, booster dose was administered 20 days after the first immersion. Antibodies as well as protective response produced in both the groups after the first and the booster immersion were different and significant (P<0.05). No significant difference was found between the species in the two age groups. The specimens immunized 8 wph showed higher antibody titres and protection than the 4 wph group. C. catla had higher relative percent survival followed by L. rohita and C. mrigala.

Detection of serum and mucosal antibody production and antibody secreting cells (ASCs) in large yellow croaker (Pseudosciaena crocea) following vaccination with Vibrio harveyi via different routes

The kinetics of mucosal and serum antibody response is well as antibody secreting cells (ASCs) production were studied in large yellow croaker following vaccination with inactivated Vibrio harveyi by different routes: oral administration. intraperitoneal (IP) injection and immersion. Indirect ELISA was used to measure the antibody level in serum and cutaneous mucus, and ELISPOT was used to monitor the ASCs derived from gill, blood and head kidney. The data demonstrated that IP injection resulted in the highest antibody levels in the systemic circulation, whereas immersion induced significant antibody levels in mucous. As for the ASCs response, IP injection induced high numbers of ASCs in the head kidney and blood; oral intubation only induced a slight ASCs response in the head kidney: immersion induced a much stronger ASCs response in the gill. These results indicate that mucosal antibodies following immersion immunization are independent of a systemic response and more sensitive, since it could be triggered earlier than serum antibodies. The mucosal antibodies following IP injection immunization may depend oil a systemic immune response. The protective effects of the three vaccination methods were compared by challenging with live V. harveyi. Survival of the three groups of vaccinated fish varied front 40 to 60%. while 100% mortality was found in control fish. Compared with IP and oral vaccination, immersion stimulated higher specific antibody titers in the mucosal system and achieved similar protection, so it is in effective and efficient method for immunizing a large number of fish against V harveyi (C) 2008 Elsevier B.V. All rights reserved.

Preparation and mass spectrometric study of egg yolk antibody (IgY) against rabies virus

Rabies virus was used as the antigen to immunize laying chickens. Anti-rabies virus immunoglobulin Y(IgY) was isolated from yolks of the eggs laid by these chickens using a two-step salt precipitation and one-step gel filtration protocol. The purified IgY was reduced with dithiothreitol, and heavy chains (HC) and light chains (LC) were obtained. In addition, the purified IgY was digested with pepsin and the fragment with specific antigen binding properties (Fab) was produced. Using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOFMS), the average molecular weights of IgY, HC, LC, and Fab were determined as 167 250, 65 105, 18 660, and 45,359 Da, respectively. IgY has two structural differences compared with mammalian IgGs. First, the molecular weight of the heavy chain of IgY is larger than that of its mammalian counterpart, while the molecular weight of the light chain of IgY is smaller. Second, upon pepsin digestion, anti-rabies virus IgY is degraded into Feb, in contrast to mammalian IgG, which has been reported to be degraded into F(ab')(2) under the same conditions. Copyright (C) 2001 John Wiley & Sons, Ltd.

Bacteremic pneumonia before and after withdrawal of 13-valent pneumococcal conjugate vaccine from a public vaccination program in Spain: a case-control study

The objective of this study is to compare the incidence and epidemiology of bacteremic community-acquired pneumonia (CAP) in the setting of changes in 13-valent pneumococcal conjugate vaccine (PCV13) coverage. In the region of Madrid, universal immunization with the PCV13 started in May 2010. In July 2012, public funding ceased. Vaccination coverage decreased from >95% to 82% in 2013 and to 67% in 2014. We performed a multicenter surveillance and case-control study from 2009-2014. Cases were hospitalized children with bacteremic CAP. Controls were children selected 1:1 from next-admitted with negative blood cultures and typical, presumed bacterial CAP. Annual incidence of bacteremic CAP declined from 7.9/100 000 children (95% CI 5.1-11.1) in 2009 to 2.1/100 000 children (95% CI 1.1-4.1) in 2012. In 2014, 2 years after PCV13 was withdrawn from the universal vaccination program, the incidence of bacteremic CAP increased to 5.4/100 000 children (95% CI 3.5-8.4). We enrolled 113 cases and 113 controls. Streptococcus pneumoniae caused most of bloodstream infections (78%). Empyema was associated with bacteremia (P = .003, OR 3.6; 95% CI 1.4-8.9). Simple parapneumonic effusion was not associated with bacteremia. Incomplete PCV immunization was not a risk factor for bacteremic pneumonia.

Polymeric and monomeric IgA response in serum and milk after parenteral cholera and oral typhoid vaccination

SCOPUS: ar.j

Equal IgG antibody response to pneumococcal vaccination in all stages of human immunodeficiency virus disease.

To evaluate the immunogenicity and safety of a 23-valent pneumococcal vaccine in human immunodeficiency virus (HIV)-seropositive patients, 80 men and 18 women received 1 dose of the vaccine (Pneumo 23; Pasteur Mérieux MSD, Brussels). The total IgG antibody response against all 23 Streptococcus pneumoniae capsular antigens was measured. Antibody levels were expressed in arbitrary units per microliter, referring to a standard curve. Geometric mean titers of the total IgG capsular antibodies on the day of vaccination and 30-45 days later were compared. The ratios of titers after and before vaccination in patients with > 500, 200-500, and < 200 CD4 lymphocytes/microL were 10, 10, and 12.6, respectively. Nonresponse (ratio < 4) occurred in 17% of patients and was unrelated to CD4 cell count. The vaccine was well tolerated; no serious side effects occurred. In 83% of the patients with HIV infection, the total antipneumococcal IgG level was higher after vaccination.

Influenza vaccination of household contacts of newborns: a hospital-based strategy to increase vaccination rates.

We implemented a hospital-based influenza vaccination program for household contacts of newborns. Among mothers not vaccinated prenatally, 44.7% were vaccinated through the program, as were 25.7% of fathers. A hospital-based program provided opportunities for vaccination of household contacts of newborns, thereby facilitating better adherence to national vaccination guidelines.

Impact of coverage-dependent marginal costs on optimal HPV vaccination strategies.

The effectiveness of vaccinating males against the human papillomavirus (HPV) remains a controversial subject. Many existing studies conclude that increasing female coverage is more effective than diverting resources into male vaccination. Recently, several empirical studies on HPV immunization have been published, providing evidence of the fact that marginal vaccination costs increase with coverage. In this study, we use a stochastic agent-based modeling framework to revisit the male vaccination debate in light of these new findings. Within this framework, we assess the impact of coverage-dependent marginal costs of vaccine distribution on optimal immunization strategies against HPV. Focusing on the two scenarios of ongoing and new vaccination programs, we analyze different resource allocation policies and their effects on overall disease burden. Our results suggest that if the costs associated with vaccinating males are relatively close to those associated with vaccinating females, then coverage-dependent, increasing marginal costs may favor vaccination strategies that entail immunization of both genders. In particular, this study emphasizes the necessity for further empirical research on the nature of coverage-dependent vaccination costs.

Modulation of the infant immune responses by the first pertussis vaccination

info:eu-repo/semantics/nonPublished

Modulation of the infant immune responses by the first pertussis vaccination

info:eu-repo/semantics/nonPublished