Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 31
Filter
1.
Intern Med J ; 2022 Jul 18.
Article in English | MEDLINE | ID: covidwho-1978479

ABSTRACT

BACKGROUND: The development of vaccines against SARS-CoV2 has been a key public health response to the COVID-19 pandemic. However, since their introduction, there have been reports of anaphylactic reactions to vaccines in individuals with history of allergic reactions to other vaccines, excipients or to COVID vaccines. AIM: A dedicated adult COVID vaccine allergy clinic with a standardised allergy testing protocol was set up to investigate safety and suitability of available COVID vaccines in Australia. METHODS: Patients referred to a state-wide COVID-19 vaccine allergy clinic between March and August 2021 with a history of allergy underwent skin-prick testing and intradermal testing to both available vaccine formulations (BNT162b2 and ChAdOx1-S), excipients (polyethylene glycol and polysorbate 80), excipient-containing medications and controls. Basophil activation testing was conducted in few subjects with convincing history of immediate type reactions. RESULTS: Fifty-three patients underwent testing for possible excipient allergy (n = 19), previous non-COVID vaccine reaction (n = 13) or previous reaction to dose 1 of COVID-19 vaccine (n = 21). Patients were predominantly female (n = 43, 81%), aged 18-83 (median 54) years. Forty-four patients tested negative and 42 of these received at least their first dose of a COVID-19 vaccine. Nine patients tested positive to excipients or excipient-containing medication only (n = 3), or vaccines (n = 6). Five patients were positive to just BNT162b2, 3/5 have been vaccinated with ChAdOx1-S. One who was skin test positive to both vaccines, but negative BAT to ChAdOx1-S was successfully vaccinated with ChAdOx1-S. CONCLUSION: Even in a high-risk population, most patients can be vaccinated with available COVID-19 vaccines. This paper reports local experiences using a combined allergy testing protocol with skin testing and BAT during the pandemic.

2.
Acta Biomater ; 148: 133-141, 2022 08.
Article in English | MEDLINE | ID: covidwho-1885570

ABSTRACT

Microneedles can realize the intradermal and transdermal delivery of drugs. However, most conventional microneedles made of metal, polymer and ceramics are unsuitable for the delivery of mRNA drugs that are fragile and temperature-sensitive. This study explores the usage of cryomicroneedles (CryoMNs) for the intradermal delivery of mRNA molecules. Taking luciferase mRNA as an example, we first optimize the formulation of CryoMNs to maximize mRNA stability. Later, in the mouse model, we compare the delivery efficiency with the conventional subcutaneous injection for both the luciferase mRNA and COVID-19 Comirnaty mRNA vaccines, where CryoMNs delivered mRNA vaccines successfully induce specific B-cell antibody, neutralizing activity and T-cell responses. STATEMENT OF SIGNIFICANCE: mRNA vaccines are fragile and temperature-sensitive, so they are mainly delivered by intramuscular injection that often causes pain and requires clinical expertise to immunize patients. Microneedles permit convenient, fast and safe vaccination. However, existing microneedle platforms are ineffective to protect the integrity of mRNA vaccines in fabrication, storage, and administration. This work utilizes cryomicroneedles (CryoMNs) technology to intradermally deliver mRNA. In the mouse model, CryoMNs are compared with the subcutaneous injection for the delivery efficiency of both the luciferase mRNA and COVID-19 Comirnaty mRNA vaccines, where CryoMNs delivered mRNA vaccines successfully produce specific B-cell antibodies, T-cell responses, and neutralizing activity. This work is expected to provide a new delivery strategy for the emerging mRNA therapeutics.


Subject(s)
COVID-19 , Animals , COVID-19/prevention & control , Drug Delivery Systems , Injections, Intradermal , Mice , Needles , RNA, Messenger/genetics , Vaccination
3.
Topics in Antiviral Medicine ; 30(1 SUPPL):92, 2022.
Article in English | EMBASE | ID: covidwho-1880648

ABSTRACT

Background: The 2-dose inactivated COVID-19 vaccine manufactured by Sinovac (CoronaVac) and viral vector COVID-19 vaccine by AstraZeneca (ChAdOx1) may not be effective in preventing Delta variant particularly after several month due to antibody decline. A 3rd dose as a booster is needed to maintain adequate antibody levels. Intradermal route is found highly immunogenic and would increase accessibility in the time of vaccine shortage. Methods: This prospective study conducted in volunteers who had received 2 doses of CoronaVac and ChAdOx1 for 6-12 weeks earlier. We investigated the immunogenicity of a booster vaccination by intramuscular administration (IM) of ChAdOx1, BNT162b2 [15 μ g], and BNT162b2 [30 μ g];and compare these with the 1/5 IM doses by intradermal (ID) route of ChAdOx1 (1x1010 viral particles, 0.1 ml) and BNT162b2 [5 μ g]. The level of anti-SARS-CoV-2 receptor binding domain (RBD) IgG were measured by chemiluminescent microparticle immunoassay (CMIA;Abbott Laboratories Ltd.) on the day of booster vaccination and 14 days after. Results: Among those received prior 2-dose CoronaVac, the geometric mean (GM) anti-SARS-CoV-2 RBD IgG level was highest following 30 μ g BNT162b2 IM boosting (5,152 BAU/mL) and followed by 15 μ g BNT162b2 IM (3,981 BAU/mL). The anti-SARS-CoV-2 RBD IgG GM level following the ID administration of 5 μ g BNT162b2 was 3,209 BAU/mL, which is not significantly different from the 15 μ g BNT162b2 IM. The IgG GM level induced by ChAdOx1 ID administration (2,810 BAU/mL) was higher than IM administration (1,358 BAU/mL). The anti-RBD IgG following booster vaccination in those prior received 2-dose ChAdOx1 primary series. Following the 30 μ g BNT162b2 IM, the anti-RBD IgG GM level was highest (2,377 BAU/mL). The level induced by 15 μ g BNT162b2 IM (1,962 BAU/mL) was not different from that by 5 μ g BNT162b2 ID (1,490 BAU/mL). The homologous 3rd dose ChAdOx1 IM and ID induced low antibody levels. Interestingly, the anti-RBD IgG levels after the 3rd dose booster in ChAdOx1 prime were generally lower than those in CoronaVac prime series. Conclusion: Heterologous boosting with BNT162b2 or ChAdOx1 induced high anti-RBD IgG levels. The intradermal route using 1/5 of intramuscular dose induced 25-156 times higher than pre-boost level, 8-31 times of the levels after 2-dose CoronaVac, and 5-8 times of that after 2-dose ChAdOx1.

4.
Int J Physiol Pathophysiol Pharmacol ; 14(2): 129-133, 2022.
Article in English | MEDLINE | ID: covidwho-1871424

ABSTRACT

COVID-19 immunization has been shown to be effective in the prevention of COVID-19. Traditionally, two vaccination doses given by intramuscular injection are required. Many scientists present ideas for an alternative administration of COVID-19 for reducing the cost and solving the problem of insufficient COVID-19 vaccine supply. Regarding the new alternative vaccine administration, the important consideration is on cost, utility and safety. Herein, we performed cost-utility-safety analysis of alternative intradermal versus classical intramuscular COVID-19 vaccination. From cost analysis, a 80% cost reduction was derived from using intradermal COVID-19 vaccine administration comparing to intramuscular vaccination. Additional, cost-utility and cost-safety analysis also show that the cost per utility and cost per safety values for intradermal vaccination are lower than those of intramuscular vaccination. According to current research, intradermal immunization is a viable alternative to traditional intramuscular COVID-19 vaccine and may even be superior.

5.
Vaccine ; 40(24): 3320-3329, 2022 05 26.
Article in English | MEDLINE | ID: covidwho-1815246

ABSTRACT

BACKGROUND: Currently, booster dose is needed after 2 doses of non-live COVID-19 vaccine. With limited resources and shortage of COVID-19 vaccines, intradermal(ID) administration might be a potential dose-sparing strategy. OBJECTIVE: To determine immunologic response and reactogenicity of ID ChAdOx1 nCoV-19 vaccine (AZD1222,Oxford/AstraZeneca) as a booster dose after completion of 2-dose CoronaVac(SV) in healthy adult. METHODS: This is a prospective cohort study of adult aged 18-59 years who received 2-dose SV at 14-35 days apart for more than 2 months. Participants received ID AZD1222 at fractional low dose(1×1010 viral particles,0.1 ml). Antibody responses were evaluated by surrogate virus neutralization test(sVNT) against delta variant and wild type, and anti-spike-receptor-binding-domain immunoglobulin G(anti-S-RBD IgG) at prior, day14, 28, 90, and 180 post booster. Solicited reactogenicity was collected for 7 days post-booster. Primary endpoint was the differences of sVNT against delta strain ≥ 80% inhibition at day14 and 90 compared with the parallel cohort study of 0.5-ml intramuscular(IM) route. RESULTS: From August2021, 100 adults with median age of 46 years(IQR 41-52) participated. Prior to booster, geometric mean(GM) of sVNT against delta strain was 22.4% inhibition(95 %CI 18.7-26.9) and of anti-S-RBD IgG was 109.3 BAU/ml(95.4-125.1). Post ID booster, GMs of sVNT against delta strain were 95.5% inhibition (95%CI 94.2-96.8) at day14, 73.1% inhibition (66.7-80.2) at day90, and 22.7% inhibition (14.9-34.6) at day180. The differences of proportion of participants achieving sVNT against delta strain ≥ 80% inhibition in ID recipients versus IM were + 4.2% (95 %CI -2.0to10.5) at day14, and -37.3%(-54.2to-20.3) at day90. Anti-S-RBD IgG GMs were 2037.1 BAU/ml (95%CI 1770.9-2343.2) at day14 and 744.6 BAU/ml(650.1-852.9) at day90, respectively. Geometric mean ratios(GMRs) of anti-S-RBD IgG were 0.99(0.83-1.20) at day14, and 0.82(0.66-1.02) at day90. Only 18% reported feverish, compared with 37% of IM (p = 0.003). Common reactogenicity was erythema at injection site(53%) while 7% reported blister. CONCLUSION: Low-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity.


Subject(s)
COVID-19 Vaccines , COVID-19 , ChAdOx1 nCoV-19 , Immunogenicity, Vaccine , Adult , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/immunology , ChAdOx1 nCoV-19/immunology , Humans , Immunization, Secondary , Immunoglobulin G , Injections, Intramuscular , Middle Aged , Prospective Studies , SARS-CoV-2
6.
Vaccines (Basel) ; 10(4)2022 Apr 08.
Article in English | MEDLINE | ID: covidwho-1786092

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic continues to disrupt essential health services in 90 percent of countries today. The spike (S) protein found on the surface of the causative agent, the SARS-CoV-2 virus, has been the prime target for current vaccine research since antibodies directed against the S protein were found to neutralize the virus. However, as new variants emerge, mutations within the spike protein have given rise to potential immune evasion of the response generated by the current generation of SARS-CoV-2 vaccines. In this study, a modified, HexaPro S protein subunit vaccine, delivered using a needle-free high-density microarray patch (HD-MAP), was investigated for its immunogenicity and virus-neutralizing abilities. Mice given two doses of the vaccine candidate generated potent antibody responses capable of neutralizing the parental SARS-CoV-2 virus as well as the variants of concern, Alpha and Delta. These results demonstrate that this alternative vaccination strategy has the potential to mitigate the effect of emerging viral variants.

7.
Vaccine ; 40(21): 2960-2969, 2022 05 09.
Article in English | MEDLINE | ID: covidwho-1773836

ABSTRACT

The enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of T cells and antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens.


Subject(s)
COVID-19 , Vaccines, DNA , Viral Vaccines , Animals , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Macaca mulatta , Mice , Mice, Inbred BALB C , SARS-CoV-2 , Vaccination
8.
Embase; 2021.
Preprint in English | EMBASE | ID: ppcovidwho-330416

ABSTRACT

Background: Additional SARS-CoV-2 vaccines that are safe and effective as primary vaccines and boosters remain urgently needed to combat the COVID-19 pandemic. We describe the safety and durability of the immune responses following two primary doses and a homologous booster dose of an investigational DNA vaccine (INO-4800) targeting the full-length spike antigen. Methods: Three dosage strengths of INO-4800 (0.5 mg, 1.0 mg, and 2.0 mg) were evaluated in 120 age-stratified healthy adults. Intradermal injection of INO-4800 followed by electroporation at 0 and 4 weeks preceded an optional booster 6-10.5 months after the second dose. Results: INO-4800 appeared well tolerated, with no treatment-related serious adverse events. Most adverse events were mild and did not increase in frequency with age and subsequent dosing. A durable antibody response was observed 6 months following the second dose;a homologous booster dose significantly increased immune responses. Cytokine producing T cells and activated CD8+ T cells with lytic potential were significantly increased in the 2.0 mg dose group. Conclusion: INO-4800 was well tolerated in a 2-dose primary series and as a homologous booster in all adults, including the elderly. These results support further development of INO-4800 for use as a primary vaccine and as a booster.

9.
Infection Control and Hospital Epidemiology ; 42(2):247-248, 2021.
Article in English | CAB Abstracts | ID: covidwho-1721266

ABSTRACT

Health workers (HCWs) are encouraged by WHO to wear gloves when directly caring for patients during the COVID-19 pandemic. Medical gloves are made from various polymers, including latex, nitrile rubber, polyvinyl chloride, polyurethane, and neoprene. Nitrile and rubber gloves are preferred during the COVID-19 pandemic due to better durability. Latex gloves are flexible, snug, responsive to the touch and provide moderate protection. Vinyl gloves provide moderate protection, are sensitive to the touch, but not as durable. However, nitrile gloves are chemical and puncture resistant, and offer the highest level of protection and durability. Various adverse skin reactions, including irritant contact dermatitis, allergic contact dermatitis and contact urticaria, have been reported with use of all gloves. Healthcare workers often use rubber gloves. Hypersensitivity to natural rubber latex (NRL) is increasingly being reported, with prevalence ranging from 2.8% to 17% among healthcare professionals. Healthcare workers are at increased risk of developing allergic reactions to NRLs, especially operating room staff, dental assistants, laboratory staff, hospital maintenance personnel, and medical personnel. A history of allergies, history of hand dermatitis, allergies to certain foods, female gender, and repeated exposure are risk factors for developing NRL hypersensitivity. Hypersensitivity reactions to bananas, avocados, chestnuts, kiwis and other fruits have been reported in these patients. Skin reactions include local itching, burning, stinging, contact, and generalized urticaria. The most common reaction observed was irritant contact dermatitis presenting as dry, scaly, and cracked patches. In suspected patients, a full history of allergy to balloons, gloves, barium enema, and other latex devices should be considered. The gold standard for diagnosis is skin prick testing in patients with localized symptoms and evaluation of pus-specific IgE antibodies in the presence of systemic symptoms. However, abrasion and/or use and patch testing are alternative diagnostic tests. The most effective approach to managing latex allergy is personal and environmental avoidance by considering hypoallergenic gloves. Recommendations for the prevention of allergic reactions to gloves are summarized in this review. Urticaria can be treated with antihistamines and antigen removal. H1.2 blockers may be used prior to contact with rubber devices;however, avoiding latex is superior to this process.

10.
Vaccine X ; 10: 100148, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1708053

ABSTRACT

INTRODUCTION: The necessity for an equal distribution of the COVID-19 vaccination is critical. Lower-middle and lower income countries may not be able to manufacture their vaccines, nor may they be able to afford to buy them for every inhabitant. Furthermore, the vaccination's potency may wane over time. A booster dosage is recommended. Despite this, certain areas or groups of people are still waiting for their first vaccine dosage. OBJECTIVES: The purposes of this study were to assess the safety and tolerability of patients who received a fractionated intradermal administration (ID) of PFE-BNT as a booster dose in a group of people who had previously finished full doses of Verocell and to determine the antibody response after the injection. METHODS: An open-label experiment was carried out. Participants were at least 18 years old. Participants received 6 ug of PFE-BNT vaccination through intradermal injection. The safety and adverse reactions were monitored at immediate after injection, 30 min later, day 1, day 7, and day 30. Venous blood tests for specific IgG concentration against SARS-CoV-2 spike S1 were received prior to injection and day 30. RESULTS: 42 participants completed the study. The mean age was 48 (the range; 23-62). The average duration after completing the 2nd dose of Verocell was 78.3 days (95% CI; 73.9-82.8). There was no serious adverse event. Almost 50% of participants reported minor adverse reactions on day 1 and roughly 30% still reporting on day 7. Systemic reactions were found less than 5%. The antibody level at day 30 was 16669.8 (95% CI; 3692.6-51238.9), which was 40 times higher. CONCLUSION: PFE-BNT at a dose of 6 ug (1/5 of the typical dose) was shown to be safe and well tolerated when given intradermally. The antibody reaction was very strong. The ID administration could potentially save vaccine doses.

11.
Vaccine ; 40(12): 1761-1767, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1700486

ABSTRACT

INTRODUCTION: The CoronaVac vaccine is widely used in Thailand to combat the coronavirus disease 2019 (COVID-19) pandemic. The limited immunogenicity of this vaccine is a concern, especially because of expanding delta variant outbreaks. A third boost may enhance antiviral immune responses. METHODS: This non-inferiority randomized controlled trial evaluated the immunogenicity and safety of an intradermal (ID) fractional third dose of AZD1222 vaccine compared with those of a standard intramuscular (IM) third dose. Participants were enrolled from August 9, 2021 to August 13, 2021 at Chulabhorn Hospital, Bangkok, Thailand. The eligibility criteria were age 18 years or older and prior two-dose Coronavac vaccination completed at least 2 months previously. Participants were randomly assigned to one of three groups by block randomization: (i) standard dose by IM administration (IM), (ii) 20% of the standard dose ID (ID1), or (iii) 40% of the standard dose ID (ID2). The primary endpoint was the geometric mean ratio of anti-receptor binding domain antibody in the ID1/ID2 vs. the IM groups 14 days post-vaccination. RESULTS: A total of 125 participants were randomized (IM, n = 41; ID1, n = 41; and ID2, n = 43). One participant was lost to follow-up by day 14 post-vaccination in the ID1 group. The geometric mean ratio (95% confidence interval) of anti-receptor binding domain antibody was 0.94 (0.80-1.09) in the ID1 group and 1.28 (0.95-1.74) in the ID2 group. Immunogenicity in both ID groups met the non-inferiority criteria. Local adverse events were more common in the ID groups than in the IM group but were mostly mild to moderate in severity. CONCLUSION: An ID fractional third dose of AZD1222 was non-inferior to a standard IM third dose among individuals previously vaccinated with CoronaVac. Adverse events associated with the ID fractional third dose included mild to moderate local site reactions. This vaccination strategy may help conserve vaccine supply.


Subject(s)
COVID-19 , ChAdOx1 nCoV-19 , Adolescent , Antibodies, Viral , COVID-19/prevention & control , Humans , Immunization, Secondary/adverse effects , Immunogenicity, Vaccine , SARS-CoV-2 , Thailand , Volunteers
13.
Cancer Immunology Research ; 10(1 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1677458

ABSTRACT

Despite extensive clinical evidence on the efficacy and safety of SARS-CoV-2 vaccines, there remains a paucity of data on their effectiveness in cancer patients who are actively receiving antineoplastic therapeutics. A recent study demonstrated only ∼30% of cancer patients had positive serologic test following 2 doses of FDA-authorized SARS-CoV-2 vaccines, in contrast to ∼80% positivity rate in healthy individuals, regardless of the age. Therefore, furtherinvestigation into novel approaches to boost immune response to SARS-CoV-2 vaccines in cancer patients isrequired. Our previous preclinical and clinical studies have established intratumoral IL-12 plasmid (TAVO)electroporation (EP) induces localized expression of IL-12p70, converting immune-excluded tumors into inflamedimmunogenic lesions, thereby generating objective responses in both treated and untreated, distant tumors. Basedon the enhancement of immunotherapy efficacy by IL-12, we leveraged the flexibility of our DNA plasmid-EPplatform to express SARS-CoV-2 spike protein in addition to IL-12 (CORVax12) as an intratumoral vaccine candidate which we hypothesized could not only drive anti-SARS-CoV-2 immune responses but also generate aproductive anti-tumor response. Naïve mice were vaccinated via intradermal injection of SARS-CoV-2 spike plasmidfollowed immediately by EP with or without plasmid-encoded mIL-12 on days 1 and 21. Longitudinal serum samples were collected to interrogate virus-specific cellular responses as well anti-spike IgG antibody. A surrogate viralneutralization test (sVNT) assessed serum blockade of soluble human ACE2 binding to immobilized SARS-CoV-2spike. Our data demonstrated that intradermally electroporated CORVax12 elicits significantly higher anti-SARS-CoV-2 spike IgG antibodies and neutralization when compared with EP of SARS-CoV-2 spike alone. Next, we askedif improved SARS-CoV-2 immune response may be observed when CORVax12 is incorporated into intratumoral EPin single-tumor bearing mice. CORVax12 robustly inhibited tumor growth, induced high percentages of germinal-center B cells and class switched B cells in tumor draining lymph nodes, and generated high of anti-spike IgG and neutralization antibodies. To further investigate systemic effects of this combination, we continued with contralateraltumor mice models. In both CT26 and B16-F10 tumor models, CORVax12 intratumoral EP induced strong systemicanti-tumor responses similar to IL-12 EP alone while also producing high serum levels of anti-SARS-CoV-2 spikeIgG and neutralization antibodies. Critically, this anti-viral immunity did not limit this IL-12-based intratumoral anti-tumor therapy. In summary, our preclinical data indicates that intratumoral EP of CORVax12 can induce IgGresponses to SARS-CoV-2 spike as well as apparent viral neutralizing activity all while maintaining local and systemic anti-tumor effects expected from TAVO Treatment. This combined intratumoral therapy represents a novelstrategy to address both tumor burden and anti-SARS-CoV-2 immunity in patients with cancer.

14.
Pharmaceutics ; 14(1)2022 Jan 08.
Article in English | MEDLINE | ID: covidwho-1631503

ABSTRACT

In vitro transcribed messenger ribonucleic acid (mRNA) constitutes an emerging therapeutic class with several clinical applications. This study presents a systematic comparison of different technologies-intradermal injection, microneedle injection, jet injection, and fractional laser ablation-for the topical cutaneous delivery of mRNA. Delivery of Cy5 labeled mRNA and non-labeled enhanced green fluorescent protein (eGFP) expressing mRNA was investigated in a viable ex vivo porcine skin model and monitored for 48 h. Forty 10 µm-thick horizontal sections were prepared from each skin sample and Cy5 labeled mRNA or eGFP expression visualized as a function of depth by confocal laser scanning microscopy and immunohistochemistry. A pixel-based method was used to create a semi-quantitative biodistribution profile. Different spatial distributions of Cy5 labeled mRNA and eGFP expression were observed, depending on the delivery modality; localization of eGFP expression pointed to the cells responsible. Delivery efficiencies and knowledge of delivery sites can facilitate development of efficient, targeted mRNA-based therapeutics.

15.
Front Med Technol ; 2: 571030, 2020.
Article in English | MEDLINE | ID: covidwho-1639212

ABSTRACT

DNA vaccines are considered as a third-generation vaccination approach in which antigenic materials are encoded as DNA plasmids for direct in vivo production to elicit adaptive immunity. As compared to other platforms, DNA vaccination is considered to have a strong safety profile, as DNA plasmids neither replicate nor elicit vector-directed immune responses in hosts. While earlier work found the immune responses induced by DNA vaccines to be sub-optimal in larger mammals and humans, recent developments in key synthetic DNA and electroporation delivery technologies have now allowed DNA vaccines to elicit significantly more potent and consistent responses in several clinical studies. This paper will review findings from the recent clinical and preclinical studies on DNA vaccines targeting emerging infectious diseases (EID) including COVID-19 caused by the SARS-CoV-2 virus, and the technological advancements pivotal to the improved responses-including the use of the advanced delivery technology, DNA-encoded cytokine/mucosal adjuvants, and innovative concepts in immunogen design. With continuous advancement over the past three decades, the DNA approach is now poised to develop vaccines against COVID-19, as well as other EIDs.

16.
Vaccine ; 40(6): 873-879, 2022 02 07.
Article in English | MEDLINE | ID: covidwho-1615721

ABSTRACT

Under the pandemic situation, there is an urgent need to produce and acquire sufficient quantities of prophylactic vaccines. It becomes important to devise a way to achieve reliable immunity with lower doses to distribute limited supplies of vaccines to maximum number of people very quickly. Intradermal (ID) vaccination is one such method to increase the effectiveness of vaccines. However, this method has not been widely used in general clinical practice because it is technically difficult to inject vaccines precisely into the ID tissue. Therefore, new ID delivery systems that allow reliable ID administration are under development. In this paper, we summarize its design and present the results of performance and usability testing for the Immucise™ Intradermal Injection System (Immucise™). This study showed that Immucise™ can reduce dead volume and inject drugs precisely into the ID tissues of subjects from infants to the elderly and can be used correctly and safely by healthcare professionals. This randomized controlled trial compared ID administration with Immucise™ and standard subcutaneous (SC) administration of seasonal influenza vaccine by analyzing the efficacy of the vaccine in the elderly group at 90 days and 180 days after administration. It was found that the vaccine for the ID group was as effective or more effective than that for the SC group up to 180 days later. It was also found that the geometric mean titer values, especially for B strains, were higher in the two-dose ID group than in the two-dose SC group. These findings suggest that Immucise™ is one of the best devices to distribute a small amount of vaccine quickly and widely to a larger number of people with little loss of vaccine during a pandemic.


Subject(s)
Influenza Vaccines , Influenza, Human , Aged , Antibodies, Viral , Humans , Influenza, Human/prevention & control , Injections, Intradermal/methods , Injections, Intramuscular , Vaccination/methods
17.
Am J Physiol Heart Circ Physiol ; 322(2): H319-H327, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1613119

ABSTRACT

Vascular dysfunction has been reported in adults who have recovered from COVID-19. To date, no studies have investigated the underlying mechanisms of persistent COVID-19-associated vascular dysfunction. Our purpose was to quantify nitric oxide (NO)-mediated vasodilation in healthy adults who have recovered from SARS-CoV-2 infection. We hypothesized that COVID-19-recovered adults would have impaired NO-mediated vasodilation compared with adults who have not had COVID-19. In methods, we performed a cross-sectional study including 10 (5 men/5 women, 24 ± 4 yr) healthy control (HC) adults who were unvaccinated for COVID-19, 11 (4 men/7 women, 25 ± 6 yr) healthy vaccinated (HV) adults, and 12 (5 men/7 women, 22 ± 3 yr) post-COVID-19 (PC, 19 ± 14 wk) adults. COVID-19 symptoms severity (survey) was assessed. A standardized 39°C local heating protocol was used to assess NO-dependent vasodilation via perfusion (intradermal microdialysis) of 15 mM NG-nitro-l-arginine methyl ester during the plateau of the heating response. Red blood cell flux was measured (laser-Doppler flowmetry) and cutaneous vascular conductance (CVC = flux/mmHg) was expressed as a percentage of maximum (28 mM sodium nitroprusside + 43°C). In results, the local heating plateau (HC: 61 ± 20%, HV: 60 ± 19%, PC: 67 ± 19%, P = 0.80) and NO-dependent vasodilation (HC: 77 ± 9%, HV: 71 ± 7%, PC: 70 ± 10%, P = 0.36) were not different among groups. Neither symptom severity (25 ± 12 AU) nor time since diagnosis correlated with the NO-dependent vasodilation (r = 0.46, P = 0.13; r = 0.41, P = 0.19, respectively). In conclusion, healthy adults who have had mild-to-moderate COVID-19 do not have altered NO-mediated cutaneous microvascular function.NEW & NOTEWORTHY Healthy young adults who have had mild-to-moderate COVID-19 do not display alterations in nitric oxide-mediated cutaneous microvascular function. In addition, healthy young adults who have COVID-19 antibodies from the COVID-19 vaccinations do not display alterations in nitric oxide-mediated cutaneous microvascular function.


Subject(s)
COVID-19/physiopathology , Microcirculation/physiology , Skin/blood supply , Vasodilation/physiology , Adult , COVID-19/metabolism , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Case-Control Studies , Enzyme Inhibitors/pharmacology , Female , Humans , Laser-Doppler Flowmetry , Male , Microcirculation/drug effects , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/metabolism , SARS-CoV-2 , Severity of Illness Index , Vasodilation/drug effects , Young Adult
18.
Intern Med ; 61(1): 81-86, 2022 Jan 01.
Article in English | MEDLINE | ID: covidwho-1606476

ABSTRACT

A 65-year-old man experienced cough and shortness of breath 3 days after receiving the first dose of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine. Chest X-ray revealed bilateral infiltrates, and the desaturation deteriorated rapidly. The symptoms and radiographic abnormalities rapidly improved after the initiation of corticosteroid therapy. Intradermal testing of the Pfizer-BioNTech COVID-19 vaccine showed a delayed positive reaction. Based on these findings, the patient was diagnosed with COVID-19 vaccine-induced pneumonitis. The timing of the onset of pneumonitis after vaccination and the results of intradermal testing suggest that Type IV hypersensitivity against COVID-19 vaccine may have been responsible for this clinical condition.


Subject(s)
COVID-19 Vaccines , COVID-19 , Aged , Humans , Male , RNA, Messenger , SARS-CoV-2 , Vaccines, Synthetic
19.
Emerg Microbes Infect ; 11(1): 212-226, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1585243

ABSTRACT

The recent emergence of COVID-19 variants has necessitated the development of new vaccines that stimulate the formation of high levels of neutralizing antibodies against S antigen variants. A new strategy involves the intradermal administration of heterologous vaccines composed of one or two doses of inactivated vaccine and a booster dose with the mutated S1 protein (K-S). Such vaccines improve the immune efficacy by increasing the neutralizing antibody titers and promoting specific T cell responses against five variants of the RBD protein. A viral challenge test with the B.1.617.2 (Delta) variant confirmed that both administration schedules (i.e. "1 + 1" and "2 + 1") ensured protection against this strain. These results suggest that the aforementioned strategy is effective for protecting against new variants and enhances the anamnestic immune response in the immunized population.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Immunity , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CHO Cells , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Chlorocebus aethiops , Cricetulus , Female , Humans , Macaca mulatta , Mice , Mice, Transgenic , Vaccination , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Vero Cells
20.
Vaccines (Basel) ; 9(12)2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1542808

ABSTRACT

Effective vaccine coverage is urgently needed to tackle the COVID-19 pandemic. Inactivated vaccines have been introduced in many countries for emergency usage, but have only provided limited protection. Heterologous vaccination is a promising strategy to maximise vaccine immunogenicity. Here, we conducted a phase I, randomised control trial to observe the safety and immunogenicity after an intradermal boost, using a fractional dosage (1:5) of BNT162b2 mRNA vaccine in healthy participants in Songkhla, Thailand. In total, 91 volunteers who had been administered with two doses of inactivated SARS-CoV-2 (CoronaVac) were recruited into the study, and then randomised (1:1:1) to received different regimens of the third dose. An intramuscular booster with a full dose of BNT162b2 was included as a conventional control, and a half dose group was included as reciprocal comparator. Both, immediate and delayed adverse events following immunisation (AEFI) were monitored. Humoral and cellular immune responses were examined to observe the booster effects. The intradermal booster provided significantly fewer systemic side effects, from 70% down to 19.4% (p < 0.001); however, they were comparable to local reactions with the conventional intramuscular booster. In the intradermal group after receiving only one fifth of the conventional dosage, serum Anti-RBD IgG was halved compared to the full dose of an intramuscular injection. However, the neutralising function against the Delta strain remained intact. T cell responses were also less effective in the intradermal group compared to the intramuscular booster. Together, the intradermal booster, using a fractional dose of BNT162b2, can reduce systemic reactions and provides a good level and function of antibody responses compared to the conventional booster. This favourable intradermal boosting strategy provides a suitable alternative for vaccines and effective vaccine management to increase the coverage during the vaccine shortage.

SELECTION OF CITATIONS
SEARCH DETAIL