Vaccination Against Rheumatic Heart Disease: A Review of Current Research Strategies and Challenges

Pandey, Manisha; Batzloff, Michael R.; Good, Michael F.

doi:10.1007/s11908-012-0263-7

Cited by 21 publications

(24 citation statements)

References 77 publications

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“…34,35). J8-DT is a minimal epitope vaccine candidate based on a highly conserved sequence within the C3 repeat of the M protein that can protect mice from skin and deep tissue infections caused by multiple emm strains (36).…”

Section: S Treptococcus Pyogenes (Group a Streptococcus [Gas]mentioning

confidence: 99%

Combinatorial Synthetic Peptide Vaccine Strategy Protects against Hypervirulent CovR/S Mutant Streptococci

Pandey

Mortensen

Calcutt

et al. 2016

The Journal of Immunology

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Cluster of virulence responder/sensor (CovR/S) mutant group A streptococci (GAS) are serious human pathogens of multiple M protein strains that upregulate expression of virulence factors, including the IL-8 protease Streptococcus pyogenes cell envelope proteinase (SpyCEP), thus blunting neutrophil-mediated killing and enabling ingress of bacteria from a superficial wound to deep tissue. We previously showed that a combination vaccine incorporating J8-DT (conserved peptide vaccine from the M protein) and a recombinant SpyCEP fragment protects against CovR/S mutants. To enhance the vaccine’s safety profile, we identified a minimal epitope (S2) that was the target for anti-SpyCEP Abs that could protect IL-8 from SpyCEP-mediated proteolysis. Abs from healthy humans and from mice experimentally infected with GAS also recognized S2, albeit at low titers. Native SpyCEP may be poorly immunogenic (cryptic or subdominant), and it would be to the organism’s advantage if the host did not induce a strong Ab response against it. However, S2 conjugated to diphtheria toxoid is highly immunogenic and induces Abs that recognize and neutralize SpyCEP. Hence, we describe a two-component peptide vaccine that induces Abs (anti-S2) that protect IL-8 from proteolysis and other Abs (anti-J8) that cause strain-independent killing in the presence of neutrophils. We show that either component alone is ineffectual in preventing skin infection and bacteremia due to CovR/S mutants but that the combination induces complete protection. This protection correlated with a significant influx of neutrophils to the infection site. The data strongly suggest that the lack of natural immunity to hypervirulent GAS strains in humans could be rectified by this combination vaccine.

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Section: S Treptococcus Pyogenes (Group a Streptococcus [Gas]mentioning

confidence: 99%

Combinatorial Synthetic Peptide Vaccine Strategy Protects against Hypervirulent CovR/S Mutant Streptococci

Pandey

Mortensen

Calcutt

et al. 2016

The Journal of Immunology

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“…Other vaccine candidates are being evaluated (reviewed in Ref. 11), but none have been tested for their ability to protect against pyoderma. In this article, we define a model of pyoderma involving minor scarification of mouse skin, followed by topical application of GAS.…”

Section: S Treptococcus Pyogenes (Group a Streptococcus [Gas]mentioning

confidence: 99%

A Synthetic M Protein Peptide Synergizes with a CXC Chemokine Protease To Induce Vaccine-Mediated Protection against Virulent Streptococcal Pyoderma and Bacteremia

Pandey

Langshaw

Hartas

et al. 2015

The Journal of Immunology

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Infections caused by Streptococcus pyogenes (group A Streptococcus [GAS]) are highly prevalent in the tropics, in developing countries, and in the Indigenous populations of developed countries. These infections and their sequelae are responsible for almost 500,000 lives lost prematurely each year. A synthetic peptide vaccine (J8-DT) from the conserved region of the M protein has shown efficacy against disease that follows i.p. inoculation of bacteria. By developing a murine model for infection that closely mimics human skin infection, we show that the vaccine can protect against pyoderma and subsequent bacteremia caused by multiple GAS strains, including strains endemic in Aboriginal communities in the Northern Territory of Australia. However, the vaccine was ineffective against a hypervirulent cluster of virulence responder/sensor mutant GAS strain; this correlated with the strain’s ability to degrade CXC chemokines, thereby preventing neutrophil chemotaxis. By combining J8-DT with an inactive form of the streptococcal CXC protease, S. pyogenes cell envelope proteinase, we developed a combination vaccine that is highly effective in blocking CXC chemokine degradation and permits opsonic Abs to kill the bacteria. Mice receiving the combination vaccine were strongly protected against pyoderma and bacteremia, as evidenced by a 100–1000-fold reduction in bacterial burden following challenge. To our knowledge, a vaccine requiring Abs to target two independent virulence factors of an organism is unique.

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“…Apesar de a grande maioria dos autores recomendarem a coleta da cultura de orofaringe concomitante naqueles casos em que a PRE é negativa (Webb, 1998;Woods, 1999;Linder et al, 2005;Fontes et al, 2007;Wald, 2007;Morais et al, 2009;Giraldez-Garcia et al, 2011;Regoli et al, 2011;Shulman et al, 2012 (Needham et al, 1998;Shulman, 2004;Linder et al, 2005;Samore et al, 2005;Buchbinder et al, 2007;Al-Najar, 2008;Ayanruoh et al, 2009;Sabuncu et al, 2009;Tanz et al, 2009;Deuster et al, 2010;Giraldez-Garcia et al, 2011;Llor et al, 2011;Regueras De Lorenzo et al, 2012;Pulcini et al, 2012;Litvin et al, 2012;Cardoso et al, 2013 A febre reumática (FR) aguda é uma doença inflamatória, imunomediada, não supurativa que pode ocorrer após infecção causada pelo EBHGA (Henningham, 2012;Pandey et al, 2012;Walker et al, 2014). Pode manifestarse como artrite, cardite, Coréia de Sydehan, eritema marginado ou nódulos subcutâneos (Carapetis et al, 2005;Costa et al, 2009 (Henningham, 2012;Pandey et al, 2012).…”

Section: D I I S S C C U U S S S S ã ã O Ounclassified

“…Pode manifestarse como artrite, cardite, Coréia de Sydehan, eritema marginado ou nódulos subcutâneos (Carapetis et al, 2005;Costa et al, 2009 (Henningham, 2012;Pandey et al, 2012). Quando não tratada ou tratada inadequadamente, cerca de 0,3 a 3% dos pacientes infectados com idade entre 5 e 15 anos podem desenvolver a FR (World Health Organization, 2004;Matthys et al, 2007;Costa et al, 2009;Gerber et al, 2009;Litvin et al, 2012;Pandey et al, 2012) e aproximadamente um a dois terços deles poderão desenvolver a cardite reumática (Costa et al, 2009). A exposição repetida a infecções pelo EBHGA, frequentemente, precede o desenvolvimento da FR (Henningham, 2012).…”

Section: D I I S S C C U U S S S S ã ã O Ounclassified

“…A patogênese da Febre Reumática Aguda envolve uma interação entre os fatores de virulência do EBHGA e a susceptibilidade do hospedeiro (Henningham, 2012 Carapetis et al, 2005;Costa et al, 2009;Regoli et al, 2011;Pandey et al, 2012;Brasil, 2013;Walker et al, 2014). Na América Latina, 21.000 casos de febre reumática (FR) ocorrem anualmente (Costa et al, 2009) Apesar do declínio na prevalência da FR, que vem ocorrendo, nas últimas três décadas, nos países desenvolvidos, a doença reumática do coração (DRC), secundária a febre reumática, continua a ser a doença cardíaca adquirida mais comum em crianças e adultos jovens, nos países em desenvolvimento e em populações desfavorecidas de países desenvolvidos (Pandey et al, 2012).…”

Section: D I I S S C C U U S S S S ã ã O Ounclassified

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Impacto do uso de técnicas microbiológicas para o estreptococo beta hemolítico do grupo A no diagnóstico e tratamento das faringotonsilites

Cardoso¹

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Dedico essa obra a minha família, meu bem mais precioso Ao meu marido, Rodrigo, meu primeiro e grande amor! Meu companheiro e incentivador de todas as horas.Aos meus filhos, Beatriz e Tiago, que me tornaram uma pessoa melhor e me apresentaram ao sentimento mais pleno que existe, o AMOR incondicional.Para eles e por eles busco sempre ser melhor... Aos meus pais, Ana Maria e Flávio, sempre incentivadores do meu trabalho! Pessoas maravilhosas que investiram na formação dos meus valores morais e éticos, além de sempre terem valorizado a minha educação e terem investido na minha formação. Sempre com muito amor! Graças a esses valores concluo essa etapa tão importante de minha vida... Aos meus irmãos, Andrea e Flávio, por sua amizade e companheirismo, e por sempre me admirarem e confiarem a mim os cuidados aos seus grandes tesouros, Rafael, Isabella e Gabriella. A A G G R R A A D D E E C C I I M M E E N N T T O O S S

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Vaccination Against Rheumatic Heart Disease: A Review of Current Research Strategies and Challenges

Cited by 21 publications

References 77 publications

Combinatorial Synthetic Peptide Vaccine Strategy Protects against Hypervirulent CovR/S Mutant Streptococci

Combinatorial Synthetic Peptide Vaccine Strategy Protects against Hypervirulent CovR/S Mutant Streptococci

A Synthetic M Protein Peptide Synergizes with a CXC Chemokine Protease To Induce Vaccine-Mediated Protection against Virulent Streptococcal Pyoderma and Bacteremia

Impacto do uso de técnicas microbiológicas para o estreptococo beta hemolítico do grupo A no diagnóstico e tratamento das faringotonsilites

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