Immunogenicity of two formulations of oral cholera vaccines in Thai volunteers

A formulation of oral vaccine consisting of Vibrio cholerae lipopolysaccharides (LPS), cell-bound haemagglutinin (CHA) and procholeragenoid (P), namely vaccine A, was compared with another formulation, vaccine B, prepared from killed whole vibrios plus procholeragenoid on their immunogenicity and reactogenicity in Thai male volunteers. Volunteers were randomly allocated into three groups. The first two groups received orally three doses of vaccines A and B, respectively at 14-day intervals. Volunteers in group 3 were controls and received orally 100 ml 5% (w/v) NaHCO3 also at 14-day intervals. Serum samples were collected from all volunteers before each immunization. Intestinal lavage was performed 3 to 7 days before the first dose of vaccine or placebo and 7, 21 and 45 days after the last dose. Serum vibriocidal antibodies were determined and class-specific, antigen-specific antibodies of all serum and lavage samples were assessed by indirect enzyme-linked immunosorbent assay (ELISA) using purified LPS, CHA and cholera toxin (CT) as antigens. Diarrhoea occurred in 10 and 40% of the vaccinees ingesting the vaccines A and B, respectively. The immunogenicity of the vaccine B in terms of seroconversion for vibriocidal antibodies and anti-LPS was higher than the vaccine A. Both vaccines had equal immunogenicity concerning serum anti-CT, while the vaccine A was slightly better than the vaccine B on serum anti-CHA response. The immunogenicity of the two vaccines in evoking intestinal responses was different from the systemic one.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antibody responses induced in mice immunized with recombinant adenovectors expressing chimeric proteins of various porcine pathogens

Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine Circovirus type 2 (PCV2) and Mycoplasma (M.) hyopneumoniae are swine pathogens of economic importance. Although vaccines are available for each pathogen, no commercial bivalent vaccines have been developed so far. In this study, recombinant adenovectors (AdVs) expressing proteins of each pathogen were developed and their immunogenicity tested in mice. The proteins of interest were the glycoprotein GP5 of PRRSV, the capsid (Cap) protein of PCV2b and the C-terminal portion of P97 (P97c) protein of M. hyopneumoniae that were used alone and/or in fusion which each other. Inoculation of mice with the AdVs resulted in antibody (Ab) responses specific to the immunogens. Unexpectedly, immunization with vaccines expressing P97c in fusion to either Cap or GP5 enhanced the Ab responses against Cap and GP5, suggesting an immunopotentiator effect for P97c.     

Molecular design of cholera vaccines

Cholera is still a serious public health problem in developing countries, particularly those in tropical regions. This has stimulated considerable research into the molecular analysis of pathogenesis resulting in the identification of a number of critical components required for both colonization of the gut mucosa and the disease symptoms. These components are the targets for rational molecular approaches to vaccine development.     

Intestinal secretory antibody response induced by an oral cholera vaccine in human volunteers

The ability is reported of a new oral cholera vaccine composed of Vibrio cholerae antigenic fractions to induce a serum and mucosal antibody response after three oral administrations of microgranules to 18 French volunteers according to different protocols of immunization. Specific antibodies were detected in the three different fluids studied (saliva, jejunal fluid, serum) in one third of volunteers before vaccination. An increase of specific IgA antibody level was observed in jejunal fluids of most volunteers after oral vaccination. An augmentation of specific antibodies against vaccine antigenic components was also observed in serum and in saliva after vaccination but in fewer volunteers.     

Field trial of oral cholera vaccines in Bangladesh: evaluation of anti-bacterial and anti-toxic breast-milk immunity in response to ingestion of the vaccines

In a field trial conducted in Bangladesh, ingestion of either B subunit-killed whole cell (BS-WC) or killed whole cell (WC) oral cholera vaccines by mothers was associated with a 47% reduction of the risk of cholera in their non-vaccinated children aged under 36 months. Because vaccine-induced breast-milk immunity seemed a possible explanation for these findings, we evaluated anti-lipopolysaccharide (LPS) and anti-cholera toxin (CT) IgA antibody responses in breast milk collected during the trial from 53 lactating women who ingested three doses of BS-WC, WC, or an Escherichia coli K12 strain (K12). Despite induction of moderate vibriocidal (1.4 to 2.0-fold) and anti-CT (4.5-fold) serum antibody responses, the vaccines did not elicit significant rises of anti-LPS or anti-CT IgA breast-milk antibodies. The failure of the vaccines to elicit significant levels of breast-milk anti-cholera antibodies suggests an alternative explanation for protection of young children by maternal vaccination, such as interruption of maternal-child transmission of Vibrio cholerae 01.     

Antibody response and resistance of Cyprinus carpio immunized with cyprinid herpes virus 3 (CyHV-3)

CyHV-3 (Cyprinid herpesvirus-3) is a large DNA virus that causes a fatal disease in koi and common carp. Infection with wild type or attenuated virus induces an immune response that renders the fish resistant to further virus challenges. The kinetics and affinity of the antibody response in immune fish depend on the temperature of the water. Virus-inoculated fish produce anti-CyHV-3 antibodies, which gradually decrease during 280 days post infection to a level slightly above that of na?ve fish. The protection against the virus is proportional to the titer of anti-virus antibodies in recently inoculated fish. Nevertheless, these immunized fish, even with no-longer detectable antibodies, are resistant to virus infection, probably due to the subsequent rapid response of high affinity anti-virus antibodies. The fact that anti-virus antibodies neutralize in vitro the pathogenic effects of the virus emphasizes the central role probably played by the antibodies in anti-CyHV-3 protection in vivo.     

Controlled field trial of the effectiveness of cholera and cholera El Tor vaccines in Calcutta

To assess the effectiveness of cholera vaccines, 2 controlled field trials were made in Calcutta—an endemic area—during 1964 and 1965. Three Indian vaccines of which 1 was grown on casein hydrolysate and 2 on agar, a freeze-dried vaccine from the Walter Reed Army Institute of Research (WRAIR), Washington, D.C., and an El Tor vaccine from the Philippines were used, with typhoid-paratyphoid (TAB) vaccine as a control. The 210 112 volunteers were vaccinated subcutaneously with a single dose of one of the vaccines.     

Protective activity of cholera vaccines against E1 Tor cholera vibrios

With the advent of epidemic El Tor cholera there has been concern about the value of cholera vaccine prepared from classical cholera strains.     

A controlled field trial of the effectiveness of cholera and cholera El Tor vaccines in the Philippines

A controlled field trial on some 584 000 people in an endemic cholera El Tor area in the Philippines demonstrated that cholera vaccines gave moderate protection of short duration. Injection of a single dose of vaccine prepared from either Vibrio cholerae or El Tor vibrios gave over 50% protection for the first 2 months. The immunity conferred by the V. cholerae vaccine declined rapidly after 3 to 4 months. The effectiveness of the El Tor vaccine continued for 6 months. An oil-adjuvant vaccine prepared from V. cholerae conferred an equally high degree of protection for a longer period of time, but, owing to severe vaccination reactions, its use could not be recommended.     

Adjuvant effect of DEAE-dextran on cholera vaccines

Investigations into the effectiveness of DEAE-dextran as an adjuvant of whole cell cholera vaccines (Vibrio cholerae Inaba and Ogawa serotypes) were conducted using two methods: (a) the active mouse protection test, (b) the determination of antibody production in the sera of immunized mice by measuring the level of vibriocidal antibodies, and by an enzyme-linked immunosorbent assay (ELISA). In all tests, the DEAE-dextran-adjuvanted vaccine showed an antigenicity substantially superior to that achieved without adjuvants.     

Antibody response to suckling mouse brain rabies vaccines for post exposure treatment

A new suckling mouse brain vaccine (SMBV) against rabies, produced by the Thai Red Cross Society, was compared with the well established Institut Pasteur SMBV in patients with very low risk rabies contact. The 4 regimens used were the standard daily injections with booster doses of Thai Red Cross vaccine (TRCV) and Institut Pasteur Vaccine (IPV), and a reduced dose scheme of 6 injections as used for tissue culture vaccines. The effect of 20 IU/kg of human rabies immune globulin (HRIG) was tested on each regimen, making 8 groups, a total of 122 patients. Blood samples taken on days 0, 7, 14, 28 and 91 were tested for neutralizing antibody. Only the standard IPV regimen produced antibody in every patient; all had levels greater than 0.5 IU at some stage. Two people (13%) given the standard TRCV produced no detectable antibody (less than or equal to 0.1 IU) throughout the study. The reduced dose regimens gave very low antibody levels. 7% of the IPV and 76% of the TRCV groups failed to produce antibody on any occasion. The antibody response was significantly suppressed by the administration of HRIG. Compared to the original South American SMBV, the vaccines tested induced low levels of short lived antibody. No reduction in the dosage of SMBV should be considered unless the potency of the product is adequate.     

Comparative study of reactions and serological response to cholera vaccines in a controlled field trial conducted in the USSR

This article presents the results of a comparative study of the reactogenicity and the serological response induced by a number of cholera vaccines. Conducted in the USSR on 998 adults aged 18 years and over, the study covered whole-cell heat-killed and formalin-inactivated cholera vaccines, whole-cell heat-killed El Tor vaccine, and a new partially purified toxoid preparation proposed for the immunoprophylaxis of cholera—all administered by hypodermic syringe or jet injector. The most marked reactions were found to occur with the formalin-inactivated cholera vaccine and the least marked with the partially purified toxoid. It was also established that the toxoid was no less effective than the whole-cell vaccine in inducing the intense production of antibodies to the Inaba serotype and, in somewhat lesser degree, to the Ogawa serotype of the El Tor vibrio. It was the only preparation to give rise to intense production of specific antitoxins in 95-98% of cases. The reactions to and immunogenic properties of the cholera vaccines did not show any statistically significant difference whether administered by hypodermic syringe or by jet injector.     

The state-of-the-art of approved and under-development cholera vaccines

Cholera remains a huge public health problem. Although in 1894, the first cholera vaccination was reported, an ideal vaccine that meets all the requirements of the WHO has not yet been produced. Among the different approaches used for cholera vaccination, attenuated vaccines represent a major category; these vaccines are beneficial in being able to induce a strong protective response after a single administration. However, they have possible negative effects on immunocompromised patient populations. Both the licensed CVD103-HgR and other vaccine approaches under development are detailed in this article, such as the Vibrio cholerae 638 vaccine candidate, Peru-15 or CholeraGarde^® and the VA1.3, VA1.4, IEM 108 VCUSM2 and CVD 112 vaccine candidates. In another strategy, killed V. cholerae vaccines have been developed, including Dukoral^®, mORCAX^® and Sanchol™. The killed vaccines are already sold, and they have successfully demonstrated their potential to protect populations in endemic areas or after natural disasters. However, these vaccines do not fulfill all the requirements of the WHO because they fail to confer long-term protection, are not suitable for children under two years, require more than a single dose and require a distribution chain with cold storage. Lastly, other vaccine strategies under development are summarized in this review. Among these strategies, vaccine candidates based on alternative drug delivery systems that have been reported lately in the literature are discussed, such as microparticles, proteoliposomes, LPS subunits, DNA vaccines and rice seeds containing toxin subunits. Preliminary results reported by many groups working on alternative delivery systems for cholera vaccines demonstrate the importance of new technologies in addressing old problems such as cholera. Although a fully ideal vaccine has not yet been designed, promising steps have been reported in the literature resulting in hope for the fight against cholera.     

Private demand for cholera vaccines in Beira, Mozambique

In the summer of 2005, we interviewed 996 randomly selected respondents in Beira, Mozambique concerning their willingness and ability to pay for cholera vaccine for themselves and for other household members. Respondents were told that two doses of the vaccine would be required 2 weeks apart, and that the cholera vaccine would offer excellent protection against infection for the first year following vaccination, and some protection during the second and third year after a person is vaccinated. This research was carried out in order to learn more about private demand for vaccines in a cholera-endemic area. We asked two types of valuation questions: (1) a discrete-price offer for a vaccine that could be purchased for household members and (2) a payment card designed to assess uncertainty in the respondent's demand for a vaccine for self-protection. We estimate average household willingness to pay (WTP) for cholera vaccines in Beira to be 2005 US$ 8.45. This estimate of household WTP represents the perceived private economic benefits to a household--six persons on average--of giving all members free cholera vaccines.     

Immunity in experimental cholera: effect of parenteral immunization with vaccines and toxoid

The protection conferred by parenteral cholera vaccines and cholera toxoid was determined in the rabbit ileal loop model of experimental cholera. Vibrio cholerae strains belonging to two different serotypes were employed, for immunization and challenge, to differentiate antibacterial and antitoxic immunity patterns. It was found that vaccines were protective but cholera toxoid was not, although serum antitoxin levels were high after administration of the latter. Antibacterial immunity was strictly serotype-specific, with evidence of cross-protection only between Ogawa and Inaba subtypes of serotype 1. Bivalent serotype 1 vaccines conferred protection against homologous challenge strains but immunity to Inaba infection was of shorter duration than immunity to Ogawa infection.     

Antibody response and persistence in volunteers following immunization with varying dosages of a trivalent surface antigen influenza virus vaccine

The serum antibody responses and 50% protective levels (PL50) of antibody were determined, using the SRH test, at one and twelve months post-vaccination in a group of student volunteers immunized with one of three dosages of a trivalent surface-antigen influenza virus vaccine, or with placebo. It was found that, for the H3, H1 and B haemagglutinin components present in the vaccine, a dose of 6 micrograms HA elicited high serum antibody responses at one month post-immunization. High mean antibody levels and a high incidence of volunteers with PL50 values of antibody against each of the HA components of the vaccine remained in the volunteer group twelve months later. The results are discussed in relation to the vaccine dosage used and the nature of the population immunized.