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“Omics” Technologies in Vaccine Research
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Vaccines had been produced quite a long time using conventional techniques, but crucial progress was made in vaccine development by the utilization of molecular biology and genetics methods to obtain recombinant vaccines. Two examples of successful recombinant vaccines are the hepatitis B and acellular pertussis (aP) vaccines. The hepatitis B vaccine includes a non-infectious viral subunit, hepatitis B surface antigen (HBsAg), produced recombinantly and highly purified, and the recombinant aP vaccine includes one or more components of Bordetella pertussis, namely, filamentous haemagglutinin (FHA), pertactin, fimbrial proteins types 2 and 3, as well as detoxified pertussis toxin (Serruto et al. 2009; Yılmaz et al. 2016).
Bordetella pertussis
Published in Firza Alexander Gronthoud, Practical Clinical Microbiology and Infectious Diseases, 2020
The acellular vaccine (DTaP) was introduced after 1997 and contains up to five purified antigens: pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and fimbria proteins 2 and 3. The upside of DTaP is a similar efficacy as DTwP, but lower rate of sideeffects. The downside is a shorter-term protection compared to DTwP.
Adaptive humoral immunity and immunoprophylaxis
Published in Gabriel Virella, Medical Immunology, 2019
Mixed-component vaccines. The interest in developing safer vaccines for whooping cough led to the introduction of mixed-component acellular vaccines. The acellular pertussis vaccine is constituted by a mixture of inactivated pertussis toxin, a major determinant of the clinical disease, and one or several additional bacterial proteins, including adhesins (filamentous hemagglutinin) and outer membrane proteins (pertactin). These vaccines have replaced the old vaccine prepared with killed Bordetella pertussis.
Novel approaches to reactivate pertussis immunity
Published in Expert Review of Vaccines, 2022
Bordetella pertussis causes acute respiratory disease that manifests as a spasmodic, paroxysmal cough in young adults. In very young children, it is associated with apnea and cyanosis and can lead to very severe disease and death in infants under the age of one [1]. This disease severity and frequency led to the development of a whole-cell pertussis vaccine, which was first licensed in the US in 1914, and was combined with tetanus and diphtheria toxoids (DTP vaccine) in the 1940s and introduced large scale into the pediatric immunization schedule in 1948, resulting in a marked drop in pertussis cases [2]. Nevertheless, concerns about the reactogenicity of whole-cell vaccine led to a refusal by many parents to vaccinate their children [3], which motivated manufacturers to develop in the 1980s new, less reactogenic pertussis vaccines. Sato and colleagues designed the first purified component acellular pertussis vaccine in Japan in 1981 [4]. Many other acellular vaccines were then developed and tested extensively in the 1990s [5]. These vaccines were composed of various pertussis antigens, such as the pertussis toxin (PT), filamentous hemagglutinin adhesin (FHA), and pertactin (PRN). aP vaccines showed a better safety profile when compared with wP vaccines and were effective in preventing pertussis disease, at least in the short term [6]. As a result, these new vaccines were introduced in the pediatric immunization schedules of many high-income countries [7].
DTaP5-HBV-IPV-Hib pediatric hexavalent combination vaccine for use in children from 6 weeks through to 4 years of age
Published in Expert Review of Vaccines, 2019
Pablo Obando-Pacheco, Irene Rivero-Calle, Peter Francis Raguindin, Federico Martinón-Torres
On the other hand, fimbriae antigen (FIM), PRP and diphtheria toxoid had higher antibody levels when PCV7 was administered separately. A relevant finding was that filamentous hemagglutinin antigen (FHA) did not reach the acceptability criteria in either of the hexavalent groups, with a higher response in the comparator arm [15]. This finding does not seem to interfere with protection against Pertussis, as the responses to PT, pertactin antigen (PRN) and FIM were robust and sufficient to generate protection. Incidence of both local and systemic adverse effects was similar among the three groups, with tenderness and erythema being the most frequently reported local event, and irritability the most reported systemic one. Fever <39ºC was more frequent when PCV7 was administered concomitantly with the hexavalent formulation.
Is there a potential for novel, nasal pertussis vaccines?
Published in Expert Review of Vaccines, 2021
Multi-locus sequencing has revealed additional genetic changes since the introduction of pertussis vaccines [27,28]. They mostly concern the promoter region of the PT gene and the gene coding for the surface antigen pertactin. Occasionally, PT-deficient strains have been isolated from children with whooping cough-like illness, but in those cases disease was less severe [29]. The most striking recent evolution is the occurrence of the exponentially increasing proportion of pertactin-deficient clinical isolates in countries using pertactin-containing DTaP [30]. The first pertactin-deficient B. pertussis strain was isolated in Italy soon after the introduction of pertactin-containing DTaP [31]. In this strain, pertactin deficiency was due to the insertion of IS481 in its structural gene. Subsequently, pertactin-deficient strains were isolated in other DTaP-using countries in Europe [32], as well as in the United States [33], Canada [34], Australia [35] and Japan [36], while in countries still using DTP, pertactin-deficient clones are rare [37]. Several distinct mechanisms have led to pertactin deficiency in these countries, indicating that pertactin-deficient strains emerged independently of each other and did not stem from a common ancestor. This observation is consistent with pertactin deficiency being the result of vaccine pressure by pertactin-containing DTaP. This hypothesis is further supported by the recent finding that pertactin is the only antigen present in DTaP that elicits complement-mediated bactericidal antibodies against B. pertussis [38], and that pertactin-deficient B. pertussis strains show greater fitness in DTaP-vaccinated mice than pertactin-producing strains [39,40]. Collectively, these observations strongly argue for DTaP vaccine escape mutations in currently circulating B. pertussis strains. However, there is currently no evidence that DTaP provides less protection against severe pertussis disease caused by pertactin-deficient strains, as protection against severe disease is likely due to PT-neutralizing antibodies, which are induced by DTaP vaccination.