The contribution of vaccination to global health: past, present and future

Greenwood, Brian

doi:10.1098/rstb.2013.0433

Cited by 775 publications

(604 citation statements)

References 38 publications

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“…Indeed, smallpox and rinderpest have been the only two viral diseases eradicated, after the enforcement of a series of health policy measures that included the use of LAVs (6)(7)(8). Furthermore, outbreaks of measles have been relatively limited because of the use of an effective live vaccine (9).…”

Section: Discussionmentioning

confidence: 99%

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Synonymous Deoptimization of Foot-and-Mouth Disease Virus Causes Attenuation In Vivo while Inducing a Strong Neutralizing Antibody Response

Segundo

Medina

Ramírez-Medina

et al. 2016

J Virol

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Codon bias deoptimization has been previously used to successfully attenuate human pathogens, including poliovirus, respiratory syncytial virus, and influenza virus. We have applied a similar technology to deoptimize the capsid-coding region (P1) of foot-andmouth disease virus (FMDV). Despite the introduction of 489 nucleotide changes (19%), synonymous deoptimization of the P1 region rendered a viable FMDV progeny. The resulting strain was stable and reached cell culture titers similar to those obtained for wild-type (WT) virus, but at reduced specific infectivity. Studies in mice showed that 100% of animals inoculated with the FMDV A12 P1 deoptimized mutant (A12-P1 deopt) survived, even when the animals were infected at doses 100 times higher than the dose required to cause death by WT virus. All mice inoculated with the A12-P1 deopt mutant developed a strong antibody response and were protected against subsequent lethal challenge with WT virus at 21 days postinoculation. Remarkably, the vaccine safety margin was at least 1,000-fold higher for A12-P1 deopt than for WT virus. Similar patterns of attenuation were observed in swine, in which animals inoculated with A12-P1 deopt virus did not develop clinical disease until doses reached 1,000 to 10,000 times the dose required to cause severe disease in 2 days with WT A12. Consistently, high levels of antibody titers were induced, even at the lowest dose tested. These results highlight the potential use of synonymous codon pair deoptimization as a strategy to safely attenuate FMDV and further develop live attenuated vaccine candidates to control such a feared livestock disease. Our work demonstrates that newly developed codon pair bias deoptimization technologies can be applied to FMD virus to obtain attenuated strains with potential for further development as novel live attenuated vaccine candidates that may rapidly control disease without reverting to virulence.

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Section: Discussionmentioning

confidence: 99%

“…Indeed, using attenuated viral vaccines, smallpox and rinderpest viruses have been eradicated (6)(7)(8), and measles has been eliminated from some parts of the world (9). So far, no attenuated vaccine has been successfully used against FMDV.…”

Section: Foot-and-mouth Disease (Fmd) Ismentioning

confidence: 99%

Synonymous Deoptimization of Foot-and-Mouth Disease Virus Causes Attenuation In Vivo while Inducing a Strong Neutralizing Antibody Response

Segundo

Medina

Ramírez-Medina

et al. 2016

J Virol

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“…Vaccination is the most efficient and cost-effective way to prevent infectious diseases [24]. Inactivated flu vaccines have the benefit of preventing the disease, however, because of poor immune response in neonates and the elderly (over 65 years of age) and the constant need to follow changes in the viral proteins, especially HA and NA, the researchers have to look for more efficient vaccines that need no annual change but provide acceptable cross-linking immunity [25].…”

Section: Discussionmentioning

confidence: 99%

Cloning, expression and purification of hemagglutinin conserved domain (HA2) of influenza A virus, to be used in broad-spectrum subunit vaccine cocktails

Farahmand

Akbari

Kh.

et al. 2016

vacres

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Introduction: Influenza virus has several conserved peptides which have the capacity to be used as suitable candidates for appropriate and stable vaccine production against different types of influenza viruses. One of these peptides is HA2, the hemagglutinin stalk domain which mediates the membrane fusion and is conserved amongst different sub-types of influenza virus. This peptide is a good candidate for participation in vaccine structure to induce immunity and antibody production. The ensued antibody may hamper the membrane fusion and subsequently the virus propagation. Methods: The peptide sequence of HA2 from influenza virus A/Tehran/18/2010 (H1N1) was analyzed using in silico tools in order to evaluate its physicochemical properties and identification of its best immunogenic sites. The confirmed sequence was amplified and cloned into a pET28a vector and the recombinant protein was over-expressed prokaryotically and confirmed by Western blotting. Results: The bioinformatics data showed that HA2 peptide stability and immunogenicity. The generated HA2 construct was confirmed by PCR, endonuclease restriction enzyme analysis and sequencing. The expression of HA2 was confirmed by SDS-PAGE and Western blot analysis. The results on the cell lysate demonstrated the high expression of HA2 subunit of the influenza virus hemagglutinin. Conclusion: One of the disadvantages of the current flu vaccines is that they cannot produce efficient broad-spectrum cellular and humoral immune responses against all subtypes of the virus due to the genetic variation of the virus. Therefore, such a conserved protein is potentially a good candidate for production of a broad-spectrum vaccine to prevent influenza epidemics and pandemics.

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“…These are drugs for bacterial [9] and helminth infections [10,11], vaccines for pathogens of all kinds [12], and insecticides [13] and the manipulation of heritable characteristics for mosquito control [14].…”

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confidence: 99%

The science of infectious diseases

Dye

O’Garra

2014

Phil. Trans. R. Soc. B

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The United Nations (UN) Millennium Development Goals (MDGs) have provided a framework for accelerating the decline of infectious diseases, backed by a massive injection of foreign investment in low-income countries. The MDG era is credited with numerous successes: between 1990 and 2012 the proportion of people living in extreme poverty was halved, and the proportion of slum dwellers in cities is also in decline. Over 2 billion people gained access to clean drinking water. Malaria death rates fell by more than a quarter, and deaths in childhood (less than 5 years) by almost one half [1].Despite these accomplishments, infectious diseases (plus maternal and nutritional disorders) remain the commonest cause of death in the world's poorest countries, whose inhabitants still suffer greatly from diarrhoeal diseases, pneumonia, HIV/AIDS, tuberculosis, malaria and helminth infections, among others. One hundred and fifty years after Europe's 'sanitation revolution', an astonishing 2.4 billion people (more than one in three) still do not have piped drinking water, and more than 1 billion people are without sanitation. Adding to the predictable burden of endemic disease, the threat of pandemics from domestic and wild animals is ever-present and global. Under-nutrition, intimately linked to infection, still affects hundreds of millions of people worldwide. The eradication of polio and Guinea worm, repeatedly promised, hang in the balance. Infections are contributing to the growing burden of chronic diseases, notably cancers associated with hepatitis B and C viruses (liver), human papilloma virus (cervix) and Helicobacter pylori (stomach). Infectious diseases have been quelled, but they are far from conquered.After 2015, the MDGs will be replaced by a new set of goals that focus on poverty reduction and sustainable development [2,3]. Health is central to the well-being of individuals and to the development of populations, and the post-2015 agenda will put health in broad context. More explicitly than the MDGs, it will take on non-communicable diseases, nutritional disorders, mental health and injuries. There will be a marked shift in political support and funding, and infectious diseases are likely to have a lower profile. At this critical juncture, this issue of papers 1 explores the frontiers of infection biology at the level of individuals (molecular, cellular, genetic, immune) and populations (demography, ecology, epidemiology). It asks how efforts to investigate and control infections will fare in the era of sustainable development, and how science can help to meet the challenge. The introductory paper [4] sets the scene by offering, among other things, a reminder that UN development goals are part of a much longer process in public health: they are the latest and biggest, concerted effort to accelerate the demographic and epidemiological transitions, setting a course towards optimal fertility and minimal premature mortality in stable populations.Then the first group of four papers examines the disease process within ind...

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The contribution of vaccination to global health: past, present and future

Cited by 775 publications

References 38 publications

Synonymous Deoptimization of Foot-and-Mouth Disease Virus Causes Attenuation In Vivo while Inducing a Strong Neutralizing Antibody Response

Synonymous Deoptimization of Foot-and-Mouth Disease Virus Causes Attenuation In Vivo while Inducing a Strong Neutralizing Antibody Response

Cloning, expression and purification of hemagglutinin conserved domain (HA2) of influenza A virus, to be used in broad-spectrum subunit vaccine cocktails

The science of infectious diseases

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