The provisional international standard antityphoid serum

The Provisional International Standard Antityphoid Serum, prepared in 1935, provided standards of the O and the Vi antibodies, both contained in a single serum preparation, and was used for standardizing the potency of therapeutic antityphoid serum.     

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.     

Totally synthetic peptide-based immunocontraceptive vaccines show activity in dogs of different breeds

In this study we examine the immunogenicity of totally synthetic peptide-based immunocontraceptive vaccines in dogs. Seven individual epitope-based vaccines were assembled in which a different T helper (T(H)) cell epitope derived from the sequence of F protein of canine distemper virus was synthesized in tandem with a peptide representing luteinising hormone releasing hormone (LHRH). Each of the individual T(H)-LHRH peptide vaccines was inoculated subcutaneously into dogs. The results demonstrate that five of the seven peptide vaccines were able to elicit strong anti-LHRH antibody responses in beagle foxhounds accompanied by a concomitant suppression in the levels of the hormones testosterone and progesterone in the majority of the animals. A pool of these five peptides was then used to inoculate five different breeds of dogs. All animals responded with high levels of anti-LHRH antibody. An investigation of the proliferative responses of peripheral blood mononuclear cells (PBMC) obtained from inoculated dogs showed that the majority of breeds responded to each of the individual T helper cell epitope tested. The results provide a strategy for development of an immunocontraceptive vaccine for use in multiple breeds of dogs.     

Protective activity and immunogenicity of two recombinant anthrax vaccines for veterinary use

In this study, the efficacy of two experimental vaccines against Bacillus anthracis toxinaemia was evaluated in the rabbit model. A recombinant Protective Antigen (rPA) mutant and a trivalent vaccine (TV) composed by the rPA, a inactive mutant of Lethal Factor (mLF-Y728A; E735A) and a inactive mutant of Edema Factor (mEF-K346R), both emulsified with mineral oils, were evaluated for their immunogenicity and protective activity in New Zealand white rabbits. Rabbits vaccinated subcutaneously with rPA and TV rapidly produced high level of anti-PA, anti-LF and anti-EF antibodies, which were still present 6 months later. In the efficacy test, these vaccines protected 100% of rabbits challenged with B. anthracis virulent strain 0843 one week after the vaccination. Moreover, all animals vaccinated twice with rPA and TV, resisted B. anthracis infection 6 months later. Our data indicate that rPA and TV could be good vaccine candidates for inducing protection against B. anthracis infection in target animal host. They could successfully be used in an emergency with simultaneous long-acting antibiotics to halt incubating infections or during an anthrax epidemic.     

Egoistic vaccines. Altruistic vaccines

Although vaccination is above all an act of individual prevention, in the case of directly transmissible diseases the vaccination of individuals may contribute indirect protection through the group immunity effect known as collective or herd immunity. The effect is due to the reduced or absent contagiousness of immunized subjects and the reduced likelihood of encounters between contagious and receptive subjects when immunized subjects are numerous. For many diseases, a vaccination coverage of 80% is sufficient to prevent epidemics. Vaccines may be classified as strictly egoistic, strictly altruistic, or simultaneously egoistic and altruistic. Rabies vaccine, which offers 100% protection if administered in time, is an example of a strictly egoistic vaccine that offers no collective benefit. German measles vaccine is strictly altruistic, since it prevents a condition that is dangerous only during fetal development. Vaccines that are both altruistic and egoistic are numerous. Measles, diphtheria, and hepatitis vaccines are examples.     

Experimental model of oral antityphoid vaccination with live streptomycin-dependent Salmonella typhimurium in C57BL/6 mice

The present experimental model offered the opportunity to study particular aspects concerning the avirulence stability of live streptomycin-dependent (Sm D) Salmonella vaccines, under conditions resembling human enteric fever. The results seem to indicate that, in practice, the risk of reversion to a virulent form during oral antityphoid vaccination with Sm D strains remains slight even after the interruption of concomitant streptomycin administration.     

Quadruple vaccines containing pertussis and poliomyelitis vaccines

Quadruple vaccines (DTP-P), prepared by mixing crude adsorbed Salk poliomyelitis vaccines, heat-killed pertussis vaccines and adsorbed purified diphtheria and tetanus toxoids were found to be toxic for mice. However, by using purified poliomyelitis and heat-killed formalinized pertussis components, vaccines were prepared that were non-toxic. The pertussis component of these vaccines retained potency over extended periods of storage. Stable, potent DTP-P vaccines offer an excellent alternative to DTP and live poliomyelitis vaccine in the basic immunization of infants and children.     

Universal influenza vaccines: Shifting to better vaccines

Influenza virus causes acute upper and lower respiratory infections and is the most likely, among known pathogens, to cause a large epidemic in humans. Influenza virus mutates rapidly, enabling it to evade natural and vaccine-induced immunity. Furthermore, influenza viruses can cross from animals to humans, generating novel, potentially pandemic strains. Currently available influenza vaccines induce a strain specific response and may be ineffective against new influenza viruses. The difficulty in predicting circulating strains has frequently resulted in mismatch between the annual vaccine and circulating viruses. Low-resource countries remain mostly unprotected against seasonal influenza and are particularly vulnerable to future pandemics, in part, because investments in vaccine manufacturing and stockpiling are concentrated in high-resource countries. Antibodies that target conserved sites in the hemagglutinin stalk have been isolated from humans and shown to confer protection in animal models, suggesting that broadly protective immunity may be possible. Several innovative influenza vaccine candidates are currently in preclinical or early clinical development. New technologies include adjuvants, synthetic peptides, virus-like particles (VLPs), DNA vectors, messenger RNA, viral vectors, and attenuated or inactivated influenza viruses. Other approaches target the conserved exposed epitope of the surface exposed membrane matrix protein M2e. Well-conserved influenza proteins, such as nucleoprotein and matrix protein, are mainly targeted for developing strong cross-protective T cell responses. With multiple vaccine candidates moving along the testing and development pipeline, the field is steadily moving toward a product that is more potent, durable, and broadly protective than previously licensed vaccines.     

Pilus vaccines

Bacterial pili (fimbriae) are protein appendages which extend from the cell surface and serve to adhere the microorganism to body surfaces. These appendages have been isolated, purified and characterized as vaccine candidates. These vaccines stimulate an immune response which serves at least with regards to Neisseria gonorrhoeae to block the adherence of the microorganism to epithelial cells. Thus far, these vaccines have proven effective in some animal studies and in a limited number of human challenge studies. The problems that remain are: lack of broad cross reactivity of the vaccines thus far developed poor immunogenicity of the important binding ligands both in terms of quality and quantity of antibody produced and inadequate stimulation of antibody response at the local site of infection.     

Salmonella-based vaccines

There continues to be considerable interest in the development of a safe, effective, live, oral vaccine to combat typhoid fever of humans. Such a vaccine may be a derivative of the causative agent of the disease, Salmonella typhi. The prototype of such a vaccine, Ty21a, is not ideal, but no replacement for Ty21a is yet obvious. The construction and trial of bivalent vaccines, in which an attenuated Salmonella strain expresses determinants from another pathogen, awaits the development of a suitably attenuated derivative. In parallel with vaccine development programmes, a variety of techniques have been designed to effect stable association between Salmonella carrier and introduced cloned DNA.     

New vaccines

New technology is allowing the development of more effective and safer vaccines to replace old vaccines and provide protection against a wider range of diseases. The worldwide priority, however, must be to increase the uptake of existing vaccines to reduce childhood mortality and morbidity.     

Cancer vaccines

Cancer vaccines have been extensively tested in animal models, and in humans. Initial studies focused on first generation vaccines based on whole cell preparations or tumor lysates derived from autologous or allogeneic tumors. Clinical studies conducted with such candidate vaccines contributed to establish the feasibility of immunizing cancer patients against their own tumors. Significant clinical benefits were observed, both in terms of long term survival and recurrence rate, in some of these trials. More recently, however, cancer vaccines targeting well-characterized tumor-associated antigens, i.e. molecules selectively or preferentially expressed by cancer cells but not by normal cells, have been designed and tested in humans. Results obtained as of today with these second-generation vaccines suggest that they are safe and that they can elicit humoral and cellular responses against tumor-specific antigens, without inducing unacceptable clinical signs of autoimmunity. Advances in tumor biology and tumor immunity have helped to better understand the mechanisms displayed by a number of tumors to escape host immunity. This bulk of new knowledge will be used to design future cancer vaccines, which will likely target multiple TAAs, presented by different antigen presentation platforms, in association with synthetic adjuvants and/or immunostimulatory cytokines. Lastly, specific tools allowing to assess in a qualitative and quantitative manner immune responses are critically needed in order to establish correlates between clinical and immune responses in patients receiving experimental vaccines.     

RNA-based vaccines

Nucleic acid vaccines consisting of plasmid DNA, viral vectors or RNA may change the way the next generation vaccines are produced, as they have the potential to combine the benefits of live-attenuated vaccines, without the complications often associated with live-attenuated vaccine safety and manufacturing. Over the past two decades, numerous clinical trials of plasmid DNA and viral vector-based vaccines have shown them to be safe, well-tolerated and immunogenic. Yet, sufficient potency for general utility in humans has remained elusive for DNA vaccines and the feasibility of repeated use of viral vectors has been compromised by anti-vector immunity. RNA vaccines, including those based on mRNA and self-amplifying RNA replicons, have the potential to overcome the limitations of plasmid DNA and viral vectors. Possible drawbacks related to the cost and feasibility of manufacturing RNA vaccines are being addressed, increasing the likelihood that RNA-based vaccines will be commercially viable. Proof of concept for RNA vaccines has been demonstrated in humans and the prospects for further development into commercial products are very encouraging.     

Leprosy vaccines

Leprosy is the clinical manifestation of chronic infection with Mycobacterium leprae, an intracellular parasite with a predilection for skin and nerves. Disabilities and mutilations associated with this disease, which are attributable primarily to nerve involvement, have made leprosy among the most feared and stigmatizing of all diseases. It is still widespread in the warmer regions of the globe, including southern Europe, southern USA and most of the developing countries. Though widespread, the distribution of the disease in endemic regions is sparse (a prevalence rate of 1 per 1000 is high) and predominantly rural, for reasons which are not understood, but which add to the difficulty of providing effective disease control.     

Nanoparticle vaccines

Nanotechnology increasingly plays a significant role in vaccine development. As vaccine development orientates toward less immunogenic “minimalist” compositions, formulations that boost antigen effectiveness are increasingly needed. The use of nanoparticles in vaccine formulations allows not only improved antigen stability and immunogenicity, but also targeted delivery and slow release. A number of nanoparticle vaccines varying in composition, size, shape, and surface properties have been approved for human use and the number of candidates is increasing. However, challenges remain due to a lack of fundamental understanding regarding the in vivo behavior of nanoparticles, which can operate as either a delivery system to enhance antigen processing and/or as an immunostimulant adjuvant to activate or enhance immunity. This review provides a broad overview of recent advances in prophylactic nanovaccinology. Types of nanoparticles used are outlined and their interaction with immune cells and the biosystem are discussed. Increased knowledge and fundamental understanding of nanoparticle mechanism of action in both immunostimulatory and delivery modes, and better understanding of in vivo biodistribution and fate, are urgently required, and will accelerate the rational design of nanoparticle-containing vaccines.