Deploy vaccines to fight superbugs

Rappuoli, Rino; Bloom, David E.; Black, Steve

doi:10.1038/d41586-017-08323-0

Cited by 105 publications

(48 citation statements)

References 8 publications

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“…The licensure of a GAS vaccine would bring global public health benefits. Prevention of a number of clinical manifestations caused by GAS would not only lower disease burden but also reduce the prescription of antibiotics and therefore positively contribute to the fight against antimicrobial resistance (14,15). The non-M protein Combo5 vaccine contains 5 conserved GAS proteins (ADI, SCPA, SLO, SpyCEP, and TF) that have low sequence variation and high coverage among GAS isolates from different geographical regions (16).…”

Section: Discussionmentioning

confidence: 99%

Vaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing Antibodies

Rivera-Hernandez

Rhyme

Cork

et al. 2020

mBio

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Recent global advocacy efforts have highlighted the importance of development of a vaccine against group A Streptococcus (GAS). Combo5 is a non-M protein-based vaccine that provides protection against GAS skin infection in mice and reduces the severity of pharyngitis in nonhuman primates. However, Combo5 with the addition of aluminum hydroxide (alum) as an adjuvant failed to protect against invasive GAS infection of mice. Here, we show that formulation of Combo5 with adjuvants containing saponin QS21 significantly improves protective efficacy, even though all 7 adjuvants tested generated high antigen-specific IgG antibody titers, including alum. Detailed characterization of Combo5 formulated with SMQ adjuvant, a squalene-in-water emulsion containing a TLR4 agonist and QS21, showed significant differences from the results obtained with alum in IgG subclasses generated following immunization, with an absence of GAS opsonizing antibodies. SMQ, but not alum, generated strong interleukin-6 (IL-6), gamma interferon (IFN-␥), and tumor necrosis alpha (TNF-␣) responses. This work highlights the importance of adjuvant selection for non-M protein-based GAS vaccines to optimize immune responses and protective efficacy. Citation Rivera-Hernandez T, Rhyme MS, Cork AJ, Jones S, Segui-Perez C, Brunner L, Richter J, Petrovsky N, Lawrenz M, Goldblatt D, Collin N, Walker MJ. 2020. Vaccine-induced Th1-type response protects against invasive group A Streptococcus infection in the absence of opsonizing antibodies. mBio 11:e00122-20.

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Section: Discussionmentioning

confidence: 99%

Vaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing Antibodies

Rivera-Hernandez

Rhyme

Cork

et al. 2020

mBio

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“…In general, the scientific hurdles to antibiotic R&D seem to be higher than those to vaccine R&D, which makes the vaccine R&D pipeline more promising than that of antibiotics. It is claimed that no chemically novel antibiotics effective against multiple important pathogens have entered clinical use in three decades, while recombinant DNA technology, conjugate and reverse vaccinology, and adjuvants have yielded 22 new vaccines over the same time period (38).…”

Section: Randd Of Vaccines Vs Randd Of Antibiotics With Gonorrhea As Anmentioning

confidence: 99%

Toward economic evaluation of the value of vaccines and other health technologies in addressing AMR

Sevilla

Bloom

Cadarette

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

110

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We discuss the need to make economic evaluations of vaccines antimicrobial resistance (AMR)-sensitive and ways to do so. Such AMR-sensitive evaluations can play a role in value-for-money comparisons of different vaccines within a national immunization program, or in comparisons of vaccine-centric and non-vaccine-centric technologies within an anti-AMR program. In general terms, incremental cost-effectiveness ratios and rates of return and their associated decision rules are unaltered by consideration of AMR-related value. The decision metrics need to have their various health, cost, and socioeconomic terms disaggregated into resistance-related subcategories, which in turn have to be measured carefully before they are reaggregated. The fundamental scientific challenges lie primarily in quantifying the causal impact of health technologies on resistance-related health outcomes, and secondarily in ascertaining the economic value of those outcomes. We emphasize the importance of evaluating vaccines in the context of other potentially complementary and substitutable nonvaccine technologies. Complementarity implies that optimal spending on each set of interventions is positive, and substitutability implies that the ratio of spending will depend on relative value for money. We exemplify this general point through a qualitative discussion of the complementarities and (especially the) substitutability between pneumococcal conjugate vaccines and antimicrobial stewardship and between research and development (R&D) of a gonorrhea vaccine versus R&D of a gonorrhea antibiotic. We propose a roadmap for future work, which includes quantifying the causal effects of vaccination and other health technologies on short-term and long-term resistance-related outcomes, measuring the health-sector costs and broader socioeconomic consequences of resistance-related mortality and morbidity, and evaluating vaccines in the context of nonvaccine complements and substitutes.

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“…Potentially there are millions or even billions of copies of the pathogen (for some infections), thereby increasing the probability of a mutation arising that might confer resistance to antibiotics. The risk of a rare mutation occurring that allows the pathogen to resist the effect of vaccination is thus lower than it is with antibiotic treatment (Rappuoli et al, 2017).…”

Section: By Preventing Disease and The Proliferation Of Bacteriamentioning

confidence: 99%

Impact of vaccines on antimicrobial resistance

Buchy¹,

Aşçıoğlu²,

Buisson

et al. 2020

International Journal of Infectious Diseases

113

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Drivers of antimicrobial resistance: Antibiotic use drives the development and spread of resistant bacterial infections. Antimicrobial resistance (AMR) has become a prolific global issue, due to significant increases in antibiotic use in humans, livestock and agriculture, inappropriate use (under-dosing and overprescribing), and misuse of antibiotics (for viral infections where they are ineffective). Fewer new antibiotics are being developed. The problem of AMR: AMR is now considered a key threat to global health, leading to more mortality and increased healthcare costs threatening future conduct of routine medical procedures. Traditional approaches to address AMR include antibiotic stewardship, better hygiene/infection control, promoting antibiotic research and development, and restricting use for agricultural purposes. Vaccines as a tool to reduce AMR: While antibiotic development is declining, vaccine technology is growing. This review shows how vaccines can decrease AMR by preventing bacterial and viral infections, thereby reducing the use/misuse of antibiotics, and by preventing antibiotic-resistant infections. Vaccines are less likely to induce resistance. Some future uses and developments of vaccines are also discussed. Conclusions: Vaccines, along with other approaches, can help reduce AMR by preventing (resistant) infections and reducing antibiotic use. Industry and governments must focus on the development of novel vaccines and drugs against resistant infections to successfully reduce AMR.

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Deploy vaccines to fight superbugs

Cited by 105 publications

References 8 publications

Vaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing Antibodies

Vaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing Antibodies

Toward economic evaluation of the value of vaccines and other health technologies in addressing AMR

Impact of vaccines on antimicrobial resistance

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