Construction and evaluation of a whole-cell pneumococcal vaccine candidate

Mohammadzadeh, Mona; Pourakbari, Babak; Doosti, Abbas; Mahmoudi, Shima; Habibi‐Anbouhi, Mahdi; Mamishi, Setareh

doi:10.1111/jam.14079

Cited by 3 publications

(3 citation statements)

References 40 publications

(88 reference statements)

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“…Current pneumococcal polysaccharide vaccines are composed of capsular polysaccharides from the most prevalent serotypes of pneumococcus [3]. The limited vaccine coverage, replacement by non-vaccine serotypes [3] and non-encapsulated S. pneumoniae (NESp) which have been isolated from patients with invasive and non-invasive pneumococcal disease [5,6] and increasing antibiotic resistance [7] are some serious threats in the near future; Therefore, the search for new candidates for a vaccine that elicit protection against a broader range of pneumococcal strains is necessary [[8], [9], [10]]. Pneumococcal surface protein A (PspA) is a very promising candidate for novel vaccine development against pneumococcal infections [11].…”

Section: Introductionmentioning

confidence: 99%

Protective responses of an engineered PspA recombinant antigen against Streptococcus pneumoniae

Akbari

Negahdari

Faraji

et al. 2019

Biotechnology Reports

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Section: Introductionmentioning

confidence: 99%

Protective responses of an engineered PspA recombinant antigen against Streptococcus pneumoniae

Akbari

Negahdari

Faraji

et al. 2019

Biotechnology Reports

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“…Importantly, protection was conferred after intranasal vaccination without using adjuvant, which provides clear advantages in terms of ease and economy of administration, and induces site‐specific memory responses. Other groups have also investigated the possibility of using a whole‐cell nonencapsulated pneumococcal vaccine to induce serotype‐independent protection, with a vaccine developed by Malley et al . currently undergoing clinical evaluation.…”

Section: Introductionmentioning

confidence: 99%

Enhanced safety and immunogenicity of a pneumococcal surface antigen A mutant whole‐cell inactivated pneumococcal vaccine

et al. 2019

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Existing capsular polysaccharide-based vaccines against pneumococcal disease are highly effective against vaccine-included serotypes, but they are unable to combat serotype replacement. We have developed a novel pneumococcal vaccine that confers serotype-independent protection, and could therefore constitute a "universal" vaccine formulation. This preparation is comprised of whole un-encapsulated pneumococci inactivated with gamma irradiation (c-PN), and we have previously reported induction of cross-reactive immunity after nonadjuvanted intranasal vaccination. To further enhance vaccine immunogenicity and safety, we modified the pneumococcal vaccine strain to induce a stressed state during growth. Specifically, the substrate binding component of the psaBCA operon for manganese import was mutated to create a pneumococcal surface antigen A (psaA) defective vaccine strain. psaA mutation severely attenuated the growth of the vaccine strain in vitro without negatively affecting pneumococcal morphology, thereby enhancing vaccine safety. In addition, antibodies raised against vaccine preparations based on the modified strain [c-PN(DPsaA)] showed more diversified reactivity to wild-type pneumococcal challenge strains compared to those induced by the original formulation. The modified vaccine also induced comparable protective T H 17 responses in the lung, and conferred greater protection against lethal heterologous pneumococcal challenge. Overall, the current study demonstrates successful refinement of a serotype-independent pneumococcal vaccine candidate to enhance safety and immunogenicity.

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“…A second alternative is the classic whole cell vaccine (Table 1), which presents a wide variety of antigens in their native form, is self-adjuvanted by presenting toll-like receptor agonist molecules, and is a good choice of vaccine for the immunization of children in LIC due to its low manufacturing cost [69,94,95]. It is expected that in countries with a high rate of colonization in early childhood, these vaccines could reduce pneumococcal colonization in the nasopharynx, maintaining the bacterial density at a minimum [69] and preventing the spread of new serotypes.…”

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confidence: 99%

Pneumococcal Vaccines: Past Findings, Present Work, and Future Strategies

Oliveira

Miyaji

et al. 2021

Vaccines

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The importance of Streptococcus pneumoniae has been well established. These bacteria can colonize infants and adults without symptoms, but in some cases can spread, invade other tissues and cause disease with high morbidity and mortality. The development of pneumococcal conjugate vaccines (PCV) caused an enormous impact in invasive pneumococcal disease and protected unvaccinated people by herd effect. However, serotype replacement is a well-known phenomenon that has occurred after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and has also been reported for other PCVs. Therefore, it is possible that serotype replacement will continue to occur even with higher valence formulations, but the development of serotype-independent vaccines might overcome this problem. Alternative vaccines are under development in order to improve cost effectiveness, either using proteins or the pneumococcal whole cell. These approaches can be used as a stand-alone strategy or together with polysaccharide vaccines. Looking ahead, the next generation of pneumococcal vaccines can be impacted by the new technologies recently approved for human use, such as mRNA vaccines and viral vectors. In this paper, we will review the advantages and disadvantages of the addition of new polysaccharides in the current PCVs, mainly for low- and middle-income countries, and we will also address future perspectives.

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Construction and evaluation of a whole-cell pneumococcal vaccine candidate

Abstract: This candidate vaccine can overcome the limitations of available polysaccharide vaccines.

Cited by 3 publications

References 40 publications

Protective responses of an engineered PspA recombinant antigen against Streptococcus pneumoniae

Protective responses of an engineered PspA recombinant antigen against Streptococcus pneumoniae

Enhanced safety and immunogenicity of a pneumococcal surface antigen A mutant whole‐cell inactivated pneumococcal vaccine

Pneumococcal Vaccines: Past Findings, Present Work, and Future Strategies

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