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.     

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.     

Anti-fertility vaccines

Vaccines are under development for the control of fertility in males and females. This review discusses developments in anti-fertility vaccines at the National Institute of Immunology, New Delhi, India. A single injection procedure for the sterilization or castration of male animals depending on the site at which the injection is given, has passed through field testing and is expected to be on the market in the near future. Vaccines inducing antibodies against the human chorionic gonadotropin have gone through phase I trials with satisfactory results. A vaccine producing a consistently bioeffective antibody response against gonadotropin-releasing hormone is ready for phase I/II clinical trials in patients of carcinoma of prostate after due experimentation in animals and toxicology studies. Research to identify sperm antigens for incorporation into second generation vaccines is in progress.     

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.     

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.     

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.     

Melanoma vaccines

Melanoma vaccines offer new hope to patients with metastatic melanoma, although convincing survival advantages have yet to be reported. This review outlines the progress made in this exciting field of research and looks ahead to the future.     

Flavivirus vaccines

Diseases caused by flavivirus infection have been a scourge of mankind for over three centuries; with yellow fever, dengue fever and Russian spring-summer encephalitis causing epidemics resulting in thousands of fatalities. Due to the development of a safe and efficacious live-attenuated vaccine against yellow fever, this disease is no longer such a threat in countries where adequate vaccination is practised. A similarly safe and efficacious inactivated vaccine against central-European tick-borne encephalitis has also been developed and this has drastically reduced the incidence of this disease in many countries where it is endemic. In spite of these successes, the development of vaccines against other pathogenic flaviviruses, causing diseases such as dengue fever and Russian spring-summer encephalitis, have not been successful. This review attempts to summarize the development of flavivirus vaccines to date and identify areas for future improvements. Problems associated with designing flavivirus vaccines are discussed and the advantages and disadvantages of future strategies for vaccine development are considered.     

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.     

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.     

Measles vaccines

The World Health Organization has settled the goal of measles elimination in European Region by the year 2007. The proposed measles elimination strategy is to reduce an estimated proportion of susceptible individuals in the population to low levels by intensive vaccination and to maintain these low levels for some years. In this strategy, the quality of measles vaccine used for immunization is crucial. The different kinds of measles vaccines used at present in the world and novel generations of vaccines are presented.