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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Attenuated/Inactivated/Live and Vectored Vaccines".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 52457

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Special Issue Editors

Prof. Dr. Martin J. D'Souza

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Guest Editor

Department of Pharmaceutical Sciences, Mercer University, Atlanta, GA 30341, USA
Interests: bio-fabrication of microparticulate vaccines for infectious diseases and cancer
Special Issues, Collections and Topics in MDPI journals

Dr. Mohammad N. Uddin

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Guest Editor

Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA
Interests: vaccine delivery; microneedle based vaccine delivery; vaccine delivery using oral dissolving films
Special Issues, Collections and Topics in MDPI journals

Dr. Rikhav Gala

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Guest Editor

Center for Molecular Biotechnology, Newark, NJ, USA
Interests: vaccine delivery; microneedle-based vaccine delivery; vaccine delivery using oral dissolving films
Special Issues, Collections and Topics in MDPI journals

Dr. Bernadette D’Souza

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Guest Editor

Department of Pharmaceutical, Social and Administrative Sciences, McWhorter School of Pharmacy, Samford University, Birmingham, AL 35229, USA
Interests: vaccine delivery; microneedle based vaccine delivery; vaccine delivery using oral dissolving films
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Dealing with the recent impact of the coronavirus pandemic, vaccines have become a topic of every household. The overall development of robust vaccines with long-lasting efficacy has gained academic, industrial, and federal interest. Vaccines are the most effective method to prevent infectious diseases, with public immunization campaigns dramatically reducing the incidence of many life-threatening diseases and preventing an estimated 2–3 million deaths a year. Contemporary research has shown that vaccines that equip patients’ immune systems to recognize and target antigens are a promising frontier for infectious, as well as non-infectious diseases. Modern-day vaccine development is a complex process starting with antigen identification, development, and expression followed by formulation and stabilization through the manufacturing process.

To formulate effective prophylactic or therapeutic vaccines, it is becoming apparent that both the innate and adaptive immune systems must be stimulated to protect from current and future recognition of the target antigen. Further, vaccine formulation in a delivery system that has high patient acceptability, which stabilizes the vaccine and also promotes cost-effective delivery, is essential for long-term use. Vaccine stability can be improved by optimizing the composition of formulations by the addition of excipients, thus, restricting molecular mobility and preventing degradation. This Special Issue focuses on different platforms available for developing robust immunotherapies for use as vaccine candidates along with vaccine stabilizations such as lyophilization, spray drying, nanoparticles, lipid vesicles, etc., and their subsequent delivery via various routes of administration.

We encourage your submission, with a short turnaround time for publication.

Prof. Dr. Martin J. D'Souza
Dr. Mohammad N. Uddin
Dr. Rikhav Gala
Dr. Bernadette D’Souza
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Vaccine delivery
microneedle-based vaccines
oral dissolving films
microparticulate vaccines
nanoparticulate vaccines

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Published Papers (9 papers)

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Research

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18 pages, 4289 KiB

Open AccessArticle

Microneedle Delivery of an Adjuvanted Microparticulate Vaccine Induces High Antibody Levels in Mice Vaccinated against Coronavirus

by Sharon Vijayanand, Smital Patil, Devyani Joshi, Ipshita Menon, Keegan Braz Gomes, Akanksha Kale, Priyal Bagwe, Shadi Yacoub, Mohammad N. Uddin and Martin J. D’Souza

Vaccines 2022, 10(9), 1491; https://doi.org/10.3390/vaccines10091491 - 7 Sep 2022

Cited by 9 | Viewed by 3488

Abstract

This ‘proof-of-concept’ study aimed to test the microparticulate vaccine delivery system and a transdermal vaccine administration strategy using dissolving microneedles (MN). For this purpose, we formulated poly(lactic-co-glycolic) acid (PLGA) microparticles (MP) encapsulating the inactivated canine coronavirus (iCCoV), as a model antigen, along with adjuvant MP encapsulating Alhydrogel^® and AddaVax. We characterized the vaccine MP for size, surface charge, morphology, and encapsulation efficiency. Further, we evaluated the in vitro immunogenicity, cytotoxicity, and antigen-presentation of vaccine/adjuvant MP in murine dendritic cells (DCs). Additionally, we tested the in vivo immunogenicity of the MP vaccine in mice through MN administration. We evaluated the serum IgG, IgA, IgG1, and IgG2a responses using an enzyme-linked immunosorbent assay. The results indicate that the particulate form of the vaccine is more immunogenic than the antigen suspension in vitro. We found the vaccine/adjuvant MP to be non-cytotoxic to DCs. The expression of antigen-presenting molecules, MHC I/II, and their costimulatory molecules, CD80/40, increased with the addition of the adjuvants. Moreover, the results suggest that the MP vaccine is cross presented by the DCs. In vivo, the adjuvanted MP vaccine induced increased antibody levels in mice following vaccination and will further be assessed for its cell-mediated responses. Full article

(This article belongs to the Special Issue Novel Vaccine Stabilization and Delivery Technologies)

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13 pages, 2410 KiB

Open AccessArticle

Low-Temperature Multiple Micro-Dispensing on Microneedles for Accurate Transcutaneous Smallpox Vaccination

by Sang-Gu Yim, Yun-Ho Hwang, Seonyeong An, Keum-Yong Seong, Seo-Yeon Kim, Semin Kim, Hyeseon Lee, Kang-Oh Lee, Mi-Young Kim, Dokeun Kim, You-Jin Kim and Seung-Yun Yang

Vaccines 2022, 10(4), 561; https://doi.org/10.3390/vaccines10040561 - 4 Apr 2022

Cited by 4 | Viewed by 4190

Abstract

Smallpox is an acute contagious disease caused by the variola virus. According to WHO guidelines, the smallpox vaccine is administrated by scarification into the epidermis using a bifurcated needle moistened with a vaccine solution. However, this invasive vaccination method involving multiple skin punctures requires a special technique to inoculate, as well as a cold chain for storage and distribution of vaccine solutions containing a live virus. Here, we report a transcutaneous smallpox vaccination using a live vaccinia-coated microneedle (MN) patch prepared by a low-temperature multiple nanoliter-level dispensing system, enabling accurate transdermal delivery of live vaccines and maintenance of bioactivity. The live vaccinia in hyaluronic acid (HA) solutions was selectively coated on the solid MN tips, and the coating amount of the vaccine was precisely controlled through a programmed multiple dispensing process with high accuracy under low temperature conditions (2–8 °C) for smallpox vaccination. Inoculation of mice (BALB/C mouse) with the MN patch coated with the second-generation smallpox vaccine increased the neutralizing antibody titer and T cell immune response. Interestingly, the live vaccine-coated MN patch maintained viral titers at −20 °C for 4 weeks and elevated temperature (37 °C) for 1 week, highlighting improved storage stability of the live virus formulated into coated MN patches. This coated MN platform using contact dispensing technique provides a simple and effective method for smallpox vaccination. Full article

(This article belongs to the Special Issue Novel Vaccine Stabilization and Delivery Technologies)

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13 pages, 1463 KiB

Open AccessArticle

Transdermal Vaccination with the Matrix-2 Protein Virus-like Particle (M2e VLP) Induces Immunity in Mice against Influenza A Virus

by Kimberly Braz Gomes, Sucheta D’Sa, Grace Lovia Allotey-Babington, Sang-Moo Kang and Martin J. D’Souza

Vaccines 2021, 9(11), 1324; https://doi.org/10.3390/vaccines9111324 - 15 Nov 2021

Cited by 11 | Viewed by 2621

Abstract

In this study, our goal was to utilize the extracellular domain matrix-2 protein virus-like particle (M2e VLP) that has been found to be highly conserved amongst all strains of influenza and could serve as a potential vaccine candidate against influenza. Previous studies have demonstrated that the VLP of the M2e showed increased activation of innate and adaptive immune responses. Therefore, to further explore its level of efficacy and protection, this vaccine was administered transdermally and tested in a pre-clinical mouse model. The M2e VLP was encapsulated into a polymeric matrix with the addition of Alhydrogel^® and Monophosphoryl Lipid-A (MPL-A^®), together referred to as AS04. The M2e VLP formulations induced IgG titers, with increased levels of IgG1 in the M2e VLP MP groups and further elevated levels of IgG2a were found specifically in the M2e VLP MP Adjuvant group. This trend in humoral immunity was also observed from a cell-mediated standpoint, where M2e VLP MP groups showed increased expression in CD4⁺ T cells in the spleen and the lymph node and high levels of CD8⁺ T cells in the lymph node. Taken together, the results illustrate the immunogenic potential of the matrix-2 protein virus-like particle (M2e VLP) vaccine. Full article

(This article belongs to the Special Issue Novel Vaccine Stabilization and Delivery Technologies)

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21 pages, 41061 KiB

Open AccessArticle

Oral Delivery of Novel Recombinant Lactobacillus Elicit High Protection against Staphylococcus aureus Pulmonary and Skin Infections

by Na Pan, Bohui Liu, Xuemei Bao, Haochi Zhang, Shouxin Sheng, Yanchen Liang, Haiting Pan and Xiao Wang

Vaccines 2021, 9(9), 984; https://doi.org/10.3390/vaccines9090984 - 3 Sep 2021

Cited by 10 | Viewed by 3357

Abstract

Staphylococcus aureus is a leading cause of nosocomial and community-associated infection worldwide; however, there is no licensed vaccine available. S. aureus initiates infection via the mucosa; therefore, a mucosal vaccine is likely to be a promising approach against S. aureus infection. Lactobacilli, a non-pathogenic bacterium, has gained increasing interest as a mucosal delivery vehicle. Hence, we attempted to develop an oral S. aureus vaccine based on lactobacilli to cushion the stress of drug resistance and vaccine needs. In this study, we designed, constructed, and evaluated recombinant Lactobacillus strains synthesizing S. aureus nontoxic mutated α-hemolysins (Hla_H35L). The results from animal clinical trials showed that recombinant Lactobacillus can persist for at least 72 h and can stably express heterologous protein in vivo. Recombinant L. plantarum WXD234 (pNZ8148-Hla) could induce robust mucosal immunity in the GALT, as evidenced by a significant increase in IgA and IL-17 production and the strong proliferation of T-lymphocytes derived from Peyer’s patches. WXD234 (pNZ8148-Hla) conferred up to 83% protection against S. aureus pulmonary infection and significantly reduced the abscess size in a S. aureus skin infection model. Of particular interest is the sharp reduction of the protective effect offered by WXD234 (pNZ8148-Hla) vaccination in γδ T cell-deficient or IL-17-deficient mice. In conclusion, for the first time, genetically engineered Lactobacillus WXD234 (pNZ8148-Hla) as an oral vaccine induced superior mucosal immunity, which was associated with high protection against pulmonary and skin infections caused by S. aureus. Taken together, our findings suggest the great potential for a delivery system based on lactobacilli and provide experimental data for the development of mucosal vaccines for S. aureus. Full article

(This article belongs to the Special Issue Novel Vaccine Stabilization and Delivery Technologies)

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19 pages, 6321 KiB

Open AccessArticle

DNA Vaccine Administered by Cationic Lipoplexes or by In Vivo Electroporation Induces Comparable Antibody Responses against SARS-CoV-2 in Mice

by Allegra Peletta, Eakachai Prompetchara, Kittipan Tharakhet, Papatsara Kaewpang, Supranee Buranapraditkun, Teerasit Techawiwattanaboon, Tayeb Jbilou, Pratomporn Krangvichian, Sunee Sirivichayakul, Suwimon Manopwisedjaroen, Arunee Thitithanyanont, Kanitha Patarakul, Kiat Ruxrungtham, Chutitorn Ketloy and Gerrit Borchard

Vaccines 2021, 9(8), 874; https://doi.org/10.3390/vaccines9080874 - 6 Aug 2021

Cited by 17 | Viewed by 3925

Abstract

In view of addressing the global necessity of an effective vaccine in the SARS-CoV-2 pandemic, a plasmid DNA vaccine, expressing for the spike (S) protein and formulated in lipoplexes, was manufactured and tested for in vitro transfection and in vivo immunogenicity. Blank cationic liposomes of 130.9 ± 5.8 nm in size and with a zeta potential of +48 ± 12 mV were formulated using the thin-film layer rehydration method. Liposomes were complexed with pCMVkan-S at different N/P ratios. Ratios of 0.25:1 and 1:1 were selected according to their complex stability and controlled size compared to other ratios and tested in vitro for transfection studies and in vivo for immunogenicity. Both selected formulations showed enhanced neutralizing antibody responses compared to pCMVkan-S injected alone, as well as an increased T cell response. The titers observed were similar to those of intramuscular electroporation (IM-EP), which was set as an efficacy goal. Full article

(This article belongs to the Special Issue Novel Vaccine Stabilization and Delivery Technologies)

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Review

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11 pages, 805 KiB

Open AccessReview

Potential Applications of Microparticulate-Based Bacterial Outer Membrane Vesicles (OMVs) Vaccine Platform for Sexually Transmitted Diseases (STDs): Gonorrhea, Chlamydia, and Syphilis

by Christiane Chbib, Sarthak M. Shah, Rikhav P. Gala and Mohammad N. Uddin

Vaccines 2021, 9(11), 1245; https://doi.org/10.3390/vaccines9111245 - 27 Oct 2021

Cited by 11 | Viewed by 4241

Abstract

Sexually transmitted diseases (STDs) are a major global health issue. Approximately 250 million new cases of STDs occur each year globally. Currently, only three STDs (human papillomavirus (HPV), hepatitis A, and hepatitis B) are preventable by vaccines. Vaccines for other STDs, including gonorrhea, chlamydia, and syphilis, await successful development. Currently, all of these STDs are treated with antibiotics. However, the efficacy of antibiotics is facing growing challenge due to the emergence of bacterial resistance. Therefore, alternative therapeutic approaches, including the development of vaccines against these STDs, should be explored to tackle this important global public health issue. Mass vaccination could be more efficient in reducing the spread of these highly contagious diseases. Bacterial outer membrane vesicle (OMV) is a potential antigen used to prevent STDs. OMVs are released spontaneously during growth by many Gram-negative bacteria. They present a wide range of surface antigens in native conformation that possess interesting properties such as immunogenicity, adjuvant potential, and the ability to be taken up by immune cells, all of which make them an attractive target for application as vaccines against pathogenic bacteria. The major challenge associated with the use of OMVs is its fragile structure and stability. However, a particulate form of the vaccine could be a suitable delivery system that can protect the antigen from degradation by a harsh acidic or enzymatic environment. The particulate form of the vaccine can also act as an adjuvant by itself. This review will highlight some practical methods for formulating microparticulate OMV-based vaccines for STDs. Full article

(This article belongs to the Special Issue Novel Vaccine Stabilization and Delivery Technologies)

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20 pages, 942 KiB

Open AccessFeature PaperReview

Buccal and Sublingual Vaccines: A Review on Oral Mucosal Immunization and Delivery Systems

by Valeria Trincado, Rikhav P. Gala and Javier O. Morales

Vaccines 2021, 9(10), 1177; https://doi.org/10.3390/vaccines9101177 - 14 Oct 2021

Cited by 32 | Viewed by 5552

Abstract

Currently, most vaccines available on the market are for parental use; however, this may not be the best option on several occasions. Mucosal routes of administration such as intranasal, sublingual, and buccal generate great interest due to the benefits they offer. These range from increasing patient compliance to inducing a more effective immune response than that achieved through conventional routes. Due to the activation of the common mucosal immune system, it is possible to generate an effective systemic and local immune response, which is not achieved through parenteral administration. Protection against pathogens that use mucosal entry routes is provided by an effective induction of mucosal immunity. Mucosal delivery systems are being developed, such as films and microneedles, which have proven to be effective, safe, and easy to administer. These systems have multiple advantages over commonly used injections, which are simple to manufacture, stable at room temperature, painless for the patient since they do not require puncture. Therefore, these delivery systems do not require to be administered by medical personnel; in fact, they could be self-administered. Full article

(This article belongs to the Special Issue Novel Vaccine Stabilization and Delivery Technologies)

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16 pages, 933 KiB

Open AccessReview

A Review on Current COVID-19 Vaccines and Evaluation of Particulate Vaccine Delivery Systems

by Sarthak M. Shah, Hashem O. Alsaab, Mutasem M. Rawas-Qalaji and Mohammad N. Uddin

Vaccines 2021, 9(10), 1086; https://doi.org/10.3390/vaccines9101086 - 27 Sep 2021

Cited by 24 | Viewed by 5246

Abstract

First detected in Wuhan, China, a highly contagious coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also known as COVID-19, spread globally in December of 2019. As of 19 September 2021, approximately 4.5 million people have died globally, and 215 million active cases have been reported. To date, six vaccines have been developed and approved for human use. However, current production and supply capabilities are unable to meet global demands to immunize the entire world population. Only a few countries have been able to successfully vaccinate many of their residents. Therefore, an alternative vaccine that can be prepared in an easy and cost-effective manner is urgently needed. A vaccine that could be prepared in this manner, as well as can be preserved and transported at room temperature, would be of great benefit to public health. It is possible to develop such an alternative vaccine by using nano- or microparticle platforms. These platforms address most of the existing vaccine limitations as they are stable at room temperature, are inexpensive to produce and distribute, can be administered orally, and do not require cold chain storage for transportation or preservation. Particulate vaccines can be administered as either oral solutions or in sublingual or buccal film dosage forms. Besides improved patient compliance, the major advantage of oral, sublingual, and buccal routes of administration is that they can elicit mucosal immunity. Mucosal immunity, along with systemic immunity, can be a strong defense against SARS-CoV-2 as the virus enters the system through inhalation or saliva. This review discusses the possibility to produce a particulate COVID vaccine by using nano- or microparticles as platforms for oral administration or in sublingual or buccal film dosage forms in order to accelerate global vaccination. Full article

(This article belongs to the Special Issue Novel Vaccine Stabilization and Delivery Technologies)

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9 pages, 239 KiB

Open AccessReview

Challenges of Storage and Stability of mRNA-Based COVID-19 Vaccines

by Mohammad N. Uddin and Monzurul A. Roni

Vaccines 2021, 9(9), 1033; https://doi.org/10.3390/vaccines9091033 - 17 Sep 2021

Cited by 205 | Viewed by 18261

Abstract

In December 2019, a new and highly pathogenic coronavirus emerged—coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), quickly spread throughout the world. In response to this global pandemic, a few vaccines were allowed for emergency use, beginning in November 2020, of which the mRNA-based vaccines by Moderna (Moderna, Cambridge, MA, USA) and BioNTech (BioTech, Mainz, Germany)/Pfizer (Pfizer, New York, NY, USA) have been identified as the most effective ones. The mRNA platform allowed rapid development of vaccines, but their global use is limited by ultracold storage requirements. Most resource-poor countries do not have cold chain storage to execute mass vaccination. Therefore, determining strategies to increase stability of mRNA-based vaccines in relatively higher temperatures can be a game changer to address the current global pandemic and upcoming new waves. In this review, we summarized the current research strategies to enhance stability of the RNA vaccine delivery system. Full article

(This article belongs to the Special Issue Novel Vaccine Stabilization and Delivery Technologies)

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