Safety and Immunogenicity of a Recombinant Multivalent Group A Streptococcal Vaccine in Healthy Adults

Abstract

ROUP A STREPTOCOCCAL INfection and its protean complications continue to cause morbidity and mortality throughout the world. The World Health Organization has estimated that 12 million people have rheumatic heart disease, of whom 400000 die each year. 1 In addition, serious invasive infections, such as bacteremia, streptococcal toxic shock syndrome, and necrotizing fasciitis, plus the more common noninvasive infections, such as pharyngitis and impetigo, produce a significant burden of disease throughout the world. Vaccine prevention of even a fraction of these cases could have a major impact on the health of children and young adults, and potentially reduce the large economic impact of these infections. 2 Efforts to develop a vaccine to prevent group A streptococcal infections have been ongoing for more than 70 years. The surface-expressed M protein is a major protective antigen of group A streptococcus and a frequent

Seven‐Year Surveillance of North American Pediatric Group A Streptococcal Pharyngitis Isolates

“…The North American emm type data from 2000 to 2007 clearly confirm and extend our previous observation that the classic rheumatogenic types (3,5,6,14,18,19, and 29) have markedly decreased in prevalence, and in some instances completely disappeared, compared with their prevalence among pharyngeal types circulating in the 1960s when acute rheumatic fever was a common pediatric illness [3]. Of 8474 pharyngeal isolates in this study, only 1 emm type 14, 18 emm type 18, no emm type 19, and 15 emm type 29 isolates were recovered.…”

Invasive Group A Streptococcal Infections, Clinical Manifestations and Their Predictors, Montreal, 1995–2002

“…This finding is also consistent with the choice of serotypes to include in streptococcal vaccines being evaluated at the moment. The hexavalent vaccine ( 37 ) is composed of serotypes 1 , 3 , 5 , 6 , 19 , and 24 ; these types represent 38% of isolates in our study. The types in the 26-valent vaccine ( 38 ) represent 70% of our isolates.…”

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

“…The candidate vaccines, associated with neutropenia in the selected papers, included 14 live attenuated virus vaccines, 6 recombinant protein and peptide vaccines, 7 viral vectored vaccines, 1 conjugate vaccine, 1 DNA prime-Adenovirus boost vaccine, 1 canarypox virus-vectored prime- recombinant protein boost vaccine, 1 DNA vectored vaccine and 1 virus like particle (VLP) vaccine. Of the recombinant protein and peptide vaccines, 2 were formulated with aluminum adjuvants [ 13 , 14 ], 1 with both alum and CPG, a synthetic oligodeoxynucleotide that acts as a TLR 9 agonist, [ 15 , 16 ], 1 with MF59 [ 13 ], an oil in water adjuvant, and 1 was administered without an adjuvant [ 17 ]. A recombinant protein administered as a boost following priming with a virus vectored vaccine was also administered with an alum adjuvant [ 18 ].…”

“…With regard to temporal associations, a total of 19 articles described the time to detection of neutropenia following vaccine administration [ 11 , 12 , 14 , 15 , 19 – 33 ]. This ranged from detection on the day of vaccine administration (day 0) in one article [ 31 ] to detection 4 weeks post vaccination in 3 articles [ 14 , 22 , 32 ]. The two instances of neutropenia reported at day 0 occurred before vaccination and normalized 2 and 10 days later, respectively [ 31 ].…”

“…The time from diagnosis to resolution of the neutropenia was reported in 11 articles [ 11 , 14 , 19 , 23 , 25 , 28 , 30 , 31 , 34 – 36 ]. In four instances the vaccine was not considered as the cause of neutropenia; more specifically, Dieye et al [ 19 ] reported a single case deemed to be unrelated to the vaccine candidate; Durbin et al [ 34 ] noted no statistical difference between the number of vaccinees and placebo recipients that suffered neutropenia with one case linked to infection with Influenza B; Kotloff et al [ 14 ] and Taalat et al [ 28 ] both diagnosed benign ethnic neutropenia (BEN) in patients with a history of low neutrophil counts prior to vaccination. The other 7 articles reported cases of neutropenia that were probably related to vaccine administration and that resolved between 2 and 21 days after the diagnosis of neutropenia had been made.…”