Challenges in the Development, Licensure, and Use of Combination Vaccines

Postema, Alicia S.; Myers, Martin G.; Breiman, Robert F.

doi:10.1086/322560

Cited by 10 publications

(4 citation statements)

References 7 publications

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“…Also, inactivated poliovirus vaccine combined with diphtheria and TT and whole cell pertussis vaccine diminished antibody response to pertussis vaccine [ 30 ]. Conversely, whole cell pertussis vaccine combined with diphtheria toxoid boosted the immune response to individual components [ 31 , 32 ]. In our model, although the combination of OVA plus TT decreased TT-specific antibodies indicating antigenic completion, the addition of LPS potentiates IgG1 and IgG2a anti-TT antibodies while decreasing IgE antibodies revealing that LPS boost the production of anti-infectious antibodies.…”

Section: Discussionmentioning

confidence: 99%

Adsorption of Toll-Like Receptor 4 Agonist to Alum-Based Tetanus Toxoid Vaccine Dampens Pro-T Helper 2 Activities and Enhances Antibody Responses

Bortolatto

Mirotti

Rodríguez

et al. 2015

Journal of Immunology Research

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Aluminum salts gels (alum) are TLR-independent adjuvants and have been used to boost antibody responses in alum-based vaccines such as diphtheria, pertussis, and tetanus toxoid (DPT) triple vaccine. However, the pro-Th2 activity of alum-based vaccine formulations has not been fully appreciated. Here we found that alum-based tetanus toxoid (TT) vaccine was biased toward a Th-2 profile as shown by TT-induced airway eosinophilic inflammation, type 2 cytokine production, and high levels of IgE anaphylactic antibodies. The adsorption into alum of prototypic TLR4 agonists such as lipopolysaccharides (LPS) derived from Escherichia coli consistently dampened TT-induced Th2 activities without inducing IFNγ or Th1-like responses in the lung. Conversely, adsorption of monophosphoryl lipid A (MPLA) extracted from Salmonella minnesota, which is a TIR-domain-containing adapter-inducing interferon-β- (TRIF-) biased TLR4 agonist, was less effective in decreasing Th-2 responses. Importantly, in a situation with antigenic competition (OVA plus TT), TT-specific IgG1 or IgG2a was decreased compared with TT sensitization. Notably, LPS increased the production of IgG1 and IgG2a TT-specific antibodies. In conclusion, the addition of LPS induces a more robust IgG1 and IgG2a TT-specific antibody production and concomitantly decreases Th2-cellular and humoral responses, indicating a potential use of alum/TLR-based vaccines.

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Section: Discussionmentioning

confidence: 99%

Adsorption of Toll-Like Receptor 4 Agonist to Alum-Based Tetanus Toxoid Vaccine Dampens Pro-T Helper 2 Activities and Enhances Antibody Responses

Bortolatto

Mirotti

Rodríguez

et al. 2015

Journal of Immunology Research

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“…A combined vaccine is that one consists of 2 or more separate immunogens physically combined into a single product [16]. Several benefits of a combined vaccine must be fulfilled as aiming to prevent multiple diseases caused by different organisms [17] and also reducing the number of injections and therefore the degree of pain and side effect of repeated vaccination.…”

Section: Introductionmentioning

confidence: 99%

Tracing the antibody mediated acquired immunity by Foot and Mouth disease and Rift Valley Fever combined vaccine in pregnant ewes and their lambs

Gamal¹,

Soliman²,

El-Manzalawy³

2014

Vet World

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The aim of this study is to provide adequate protection to ewes and their lambs against Foot and Mouth disease (FMD) and Rift Valley Fever (RVF). Materials and Methods:A combined inactivated FMD and RVF oil vaccine was prepared successfully. Such vaccine was found to be free from foreign contaminants, safe and potent as determined by quality control tests such as challenge protection percentage for FMD and mice ED 50 for RVF. Vaccination of pregnant ewes with the prepared combined vaccine and determination of the antibody level via serum neutralization test (SNT) and Enzyme Linked immune sorbent assay (ELISA) in the vaccinated pregnant ewes and their lambs.Results: Vaccination of pregnant ewes revealed that these ewes exhibited high levels of specific antibodies against the included vaccine antigens (Foot and Mouth disease virus type A Iran O5, O PanAsia and SAT2/EGY/2012 and RVFV-ZH501). FMD antibodies recorded their peaks by the 10 th week post vaccination while those of RVF recorded their peaks by the 12 th week post vaccination then all antibodies began to decrease gradually to reach their lowest protective titers for FMD by the 32 nd week post vaccination and those for RVF by the 34 th week post vaccination. Potency test of the prepared combined vaccine expressed as protection percentage of vaccinated sheep against target virulent FMD virus serotypes reflected a protection percentage of 80% against type O and SAT2 and 100% against A while for RVF, the mice ED 50 was found to be 0.009 indicating the potency of the prepared vaccine. The antibody titer in serum and colostrum of vaccinated pregnant ewes at day of parturition (10-12 week post vaccination) recorded a high titer against FMD serotype (O), serotype (A), serotype (SAT2) and against RVF. It was noticed that the colostrum antibody titers were slightly higher than those in the sera of vaccinated ewes at time of parturition. The newly born lambs from vaccinated ewes, exhibited good levels of maternal immunity against the included antigens through suckling their mother colostrum by the 24 hrs. post parturition. The newly born lambs recorded their highest level by 1 week of birth and lasted within a protective level up to 11-12 week of birth. Conclusion:Using of FMD/RVF combined vaccine provided a sufficient immune status for pregnant ewes as well as for their lambs. Vaccination of newly born lambs should be carried out by the 4 th month of birth.

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“…Such vaccines, that combine antigens from two or more different vaccines, are often submitted for licensure on the basis of non-inferiority trials that demonstrate safety and immunogenicity profiles similar to component vaccines administered separately [15]. Combination vaccines are often proposed as a future solution that may help overcome the many ethical and regulatory issues in developing second-generation vaccines: a new antigen could be included in combination with the antigen(s) in the licensed vaccine (for example, RTS,S plus antigens).…”

Section: Discussionmentioning

confidence: 99%

Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines

Fowkes

Simpson

Beeson

2013

BMC Med

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BackgroundMalaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination.DiscussionThe Malaria Vaccine Technology Roadmap’s goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%’. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine.ConclusionsSelecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine.

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Challenges in the Development, Licensure, and Use of Combination Vaccines

Cited by 10 publications

References 7 publications

Adsorption of Toll-Like Receptor 4 Agonist to Alum-Based Tetanus Toxoid Vaccine Dampens Pro-T Helper 2 Activities and Enhances Antibody Responses

Adsorption of Toll-Like Receptor 4 Agonist to Alum-Based Tetanus Toxoid Vaccine Dampens Pro-T Helper 2 Activities and Enhances Antibody Responses

Tracing the antibody mediated acquired immunity by Foot and Mouth disease and Rift Valley Fever combined vaccine in pregnant ewes and their lambs

Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines

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