Intradermal Route Research Articles

L-DBF Elicits Cross Protection Against Different Serotypes of Shigella spp

Shigellosis is a severe diarrheal disease caused by members of the genus Shigella, with at least 80 million cases and 700,000 deaths annually around the world. The type III secretion system (T3SS) is the primary virulence factor used by the shigellae, and we have previously demonstrated that vaccination with the type T3SS proteins IpaB and IpaD, along with an IpaD/IpaB fusion protein (DBF), protects mice from Shigella infection in a lethal pulmonary model. To simplify the formulation and development of the DBF Shigella vaccine, we have genetically fused LTA1, the active subunit of heat-labile toxin from enterotoxigenic E. coli, with DBF to produce the self-adjuvanting antigen L-DBF. Here we immunized mice with L-DBF via the intranasal, intramuscular, and intradermal routes and challenged them with a lethal dose of S. flexneri 2a. While none of the mice vaccinated intramuscularly or intradermally were protected, mice vaccinated with L-DBF intranasally were protected from lethal challenges with S. flexneri 2a, S. flexneri 1b, S. flexneri 3a, S. flexneri 6, and S. sonnei. Intranasal L-DBF induced both B cell and T cell responses that correlated with protection against Shigella infection. Our results suggest that L-DBF is a candidate for developing an effective serotype-independent vaccine against Shigella spp.

Safety of PRRSV-2 MLV vaccines administrated via the intramuscular or intradermal route and evaluation of PRRSV transmission upon needle-free and needle delivery

Two distinct experiments (Exp) were conducted to evaluate the shedding and efficacy of 2 modified live porcine reproductive and respiratory syndrome virus (PRRSV) type 2 vaccines (MLV) when administered intramuscularly (IM) or intradermally (ID) (Exp A), and the potential of PRRSV transmission using a needle-free device (Exp B). One-hundred fifty-four, 3-week-old castrated-male, pigs were procured from a PRRSV-free herd. In Exp A, 112 pigs were randomly allocated into 4 groups of 21 pigs including IM/Ingelvac MLV (G1), IM/Prime Pac (G2), ID/Prime Pac (G3), and non-vaccination (G4). Twenty-eight remaining pigs were served as non-vaccination, age-matched sentinel pigs. G1 was IM vaccinated once with Ingelvac PRRS MLV (Ing) (Boehringer Ingelheim, Germany). G2 and G3 were IM and ID vaccinated once with a different MLV, Prime Pac PRRS (PP) (MSD Animal Health, The Netherlands), respectively. Following vaccination, an antibody response, IFN-γ-SC, and IL-10 secretion in supernatants of stimulated PBMC were monitored. Sera, tonsils, nasal swabs, bronchoalveolar lavage, urines, and feces were collected from 3 vaccinated pigs each week to 42 days post-vaccination (DPV) and assayed for the presence of PRRSV using virus isolation and qPCR. Age-matched sentinel pigs were used to evaluate the transmission of vaccine viruses and were introduced into vaccinated groups from 0 to 42 DPV. Seroconversion was monitored. In Exp B, 42 pigs were randomly allocated into 5 groups of 3 pigs each including IM/High (T1), ID/High (T2), IM/Low (T3), ID/Low (T4), and NoChal. Twenty-seven remaining pigs were left as non-challenge, age-matched sentinel pigs. The T1 and T2, and T3 and T4 groups were intranasally challenged at approximately 26 days of age with HP-PRRSV-2 at high (106) and low (103 TCID50/ml) doses, respectively. At 7 days post-challenge, at the time of the highest viremia levels of HP-PRRSV-2, T1 and T2, and T3 and T4 groups were IM and ID injected with Diluvac Forte using needles and a need-less device (IDAL 3G, MSD Animal Health, The Netherlands), respectively. Same needles or needle-less devices were used to inject the same volume of Diluvac Forte into sentinel pigs. Seroconversion of sentinels was evaluated. The results demonstrated that PP vaccinated groups (G2 and G3), regardless of the route of vaccination, had ELISA response significantly lower than G1 at 7 and 14 DPV. PP-vaccinated groups (G2 and G3) had significantly higher IFN-γ-SC and lower IL-10 secretion compared to the Ing-vaccinated group (G1). The two different MLV when administered intramuscularly demonstrated the difference in virus distribution and shedding patterns. PP-vaccinated pigs had significantly shortened viremia than the Ing-vaccinated pigs. However, ID-vaccinated pigs had lower virus distribution in organs and body fluids without virus shedding to sentinel pigs. In Exp B, regardless of the challenge dose, sentinel pigs intradermally injected with the same needle-less device used to inject challenged pigs displayed no seroconversion. In contrast, sentinel pigs intramuscularly injected with the same needle used to inject challenged pigs displayed seroconversion. The results demonstrated the transmission of PRRSV by using a needle, but not by using a needle-less device. In conclusion, our results demonstrated that ID vaccination might represent an alternative to improve vaccine efficacy and safety, and may be able to reduce the shedding of vaccine viruses and reduce the iatrogenic transfer of pathogens between animals with shared needles.

Life Sciences Discovery and Technology Highlights

Life Sciences Discovery and Technology Highlights

Pulmonary BCG induces lung-resident macrophage activation and confers long-term protection against tuberculosis.

Bacillus Calmette-Guerin (BCG) is an attenuated bacterial vaccine used to protect against Mycobacterium tuberculosis (Mtb) in regions where infections are highly prevalent. BCG is currently delivered by the intradermal route, but alternative routes of administration are of great interest, including intrapulmonary delivery to more closely mimic respiratory Mtb infection. In this study, mice subjected to pulmonary delivery of green fluorescent protein–tagged strains of virulent (Mtb) and attenuated (BCG) mycobacteria were studied to better characterize infected lung cell subsets. Profound differences in dissemination patterns were detected between Mtb and BCG, with a strong tendency of Mtb to disseminate from alveolar macrophages (AMs) to other myeloid subsets, mainly neutrophils and recruited macrophages. BCG mostly remained in AMs, which promoted their activation. These preactivated macrophages were highly efficient in containing Mtb bacilli upon challenge and disrupting early bacterial dissemination, which suggests a potential mechanism of protection associated with pulmonary BCG vaccination. Respiratory BCG also protected mice against a lethal Streptococcus pneumoniae challenge, suggesting that BCG-induced innate activation could confer heterologous protection against respiratory pathogens different from Mtb. BCG drove long-term activation of AMs, even after vaccine clearance, and these AMs reacted efficiently upon subsequent challenge. These results suggest the generation of a trained innate memory-like response in AMs induced by pulmonary BCG vaccination.

Synthetic SARS-CoV-2 Spike-Based DNA Vaccine Elicits Robust and Long-Lasting Th1 Humoral and Cellular Immunity in Mice.

The ongoing global pandemic of coronavirus disease 2019 (COVID-19) calls for an urgent development of effective and safe prophylactic and therapeutic measures. The spike (S) glycoprotein of severe acute respiratory syndrome-coronavirus (SARS-CoV-2) is a major immunogenic and protective protein and plays a crucial role in viral pathogenesis. In this study, we successfully constructed a synthetic codon-optimized DNA-based vaccine as a countermeasure against SARS-CoV-2, denoted VIU-1005. The design was based on a codon-optimized coding sequence of a consensus full-length S glycoprotein. The immunogenicity of the vaccine was tested in two mouse models (BALB/c and C57BL/6J). Th1-skewed systemic S-specific IgG antibodies and neutralizing antibodies (nAbs) were significantly induced in both models 4 weeks after three injections with 100 μg of the VIU-1005 vaccine via intramuscular needle injection but not intradermal or subcutaneous routes. Such immunization induced long-lasting IgG and memory T cell responses in mice that lasted for at least 6 months. Interestingly, using a needle-free system, we showed an enhanced immunogenicity of VIU-1005 in which lower or fewer doses were able to elicit significantly high levels of Th1-biased systemic S-specific immune responses, as demonstrated by the significant levels of binding IgG antibodies, nAbs and IFN-γ, TNF and IL-2 cytokine production from memory CD8+ and CD4+ T cells in BALB/c mice. Furthermore, compared to intradermal needle injection, which failed to induce any significant immune response, intradermal needle-free immunization elicited a robust Th1-biased humoral response similar to that observed with intramuscular immunization. Together, our results demonstrate that the synthetic VIU-1005 candidate DNA vaccine is highly immunogenic and capable of inducing long-lasting Th1-skewed humoral and cellular immunity in mice. Furthermore, we show that the use of a needle-free system could enhance the immunogenicity and minimize doses needed to induce protective immunity in mice, supporting further preclinical and clinical testing of this candidate vaccine.

Efficacy of Needle-Less Intradermal Vaccination against Porcine Epidemic Diarrhea Virus.

To prevent diarrhea in suckling piglets infected by porcine epidemic diarrhea virus (PEDV), porcine epidemic diarrhea (PED) vaccines are administered mainly through intramuscular (IM) or oral routes. We found that growing pigs vaccinated with an inactivated PEDV vaccine via the intradermal (ID) route had higher neutralizing antibody titers and cytokine (IFN-γ, IL-4, and IL-10) levels than non-vaccinated pigs. In addition, suckling piglets acquired lactogenic immunity from pregnant sows inoculated with an ID PED vaccine. We evaluated the efficacy of vaccination via this route, along with subsequent protection against virulent PEDV. At six days post-challenge, the survival rate of suckling piglets exposed to virulent PEDV was 70% for the ID group and 0% for the mock group (no vaccine). At necropsy, villi length in the duodenum and ileum of piglets with lactogenic immunity provided by ID-vaccinated sows proved to be significant (p < 0.05) when compared with those in piglets from mock group sows. Thus, vaccination using an inactivated PED vaccine via the ID route provides partial protection against infection by virulent PEDV.

Intranasal vaccine from whole Leishmania donovani antigens provides protection and induces specific immune response against visceral leishmaniasis.

Visceral leishmaniasis is a protozoan disease associated with high fatality rate in developing countries. Although the drug pipeline is constantly improving, available treatments are costly and live-threatening side effects are not uncommon. Moreover, an approved vaccine against human leishmaniasis does not exist yet. Using whole antigens from Leishmania donovani promastigotes (LdAg), we investigated the protective potential of a novel adjuvant-free vaccine strategy. Immunization of mice with LdAg via the intradermal or the intranasal route prior to infection decreases the parasitic burden in primary affected internal organs, including the liver, spleen, and bone marrow. Interestingly, the intranasal route is more efficient than the intradermal route, leading to better parasite clearance and remarkable induction of adaptive immune cells, notably the helper and cytotoxic T cells. In vitro restimulation experiments with Leishmania antigens led to significant IFN-γ secretion by splenocytes; therefore, exemplifying specificity of the adaptive immune response. To improve mucosal delivery and the immunogenic aspects of our vaccine strategy, we used polysaccharide-based nanoparticles (NP) that carry the antigens. The NP-LdAg formulation is remarkably taken up by dendritic cells and induces their maturation in vitro, as revealed by the increased expression of CD80, CD86 and MHC II. Intranasal immunization with NP-LdAg does not improve the parasite clearance in our experimental timeline; however, it does increase the percentage of effector and memory T helper cells in the spleen, suggesting a potential induction of long-term memory. Altogether, this study provides a simple and cost-effective vaccine strategy against visceral leishmaniasis based on LdAg administration via the intranasal route, which could be applicable to other parasitic diseases.

Anti-allergic Assessment of Ethanol Extractives of Quisqualis Indica Linn

Aim:The present work was aimed at finding out the anti-allergic activity of ethanol extracts of Quisqualis indica Linn. (EEQI) by in-vitro and in-vivo murine models.Background:Worldwide, the rise in the prevalence of allergic diseases has continued in the industrialized world for more than 50 years. About 0.05-2% of the population is estimated to experience anaphylaxis at some point in life. Quisqualis indica Linn in an ornamental plant that has been rarely used as a herbal medicine, however, the presence of polyphenols and flavonoids have been reported to possess anti-inflammatory, antipyretic and immunomodulatory activity, which have some pathological relevance with anaphylaxis.Objective:The objective of the present research was to investigate, scientifically explore and understand the probable anti-anaphylactic mechanism of ethanol extracts of Quisqualis indica Linn. via different preclinical models.Material and Method:In-vitro study was done on de-granulated mesenteric mast cells induced by compound 48/80 and in-vivo study was done by Passive Cutaneous Anaphylaxis (PCA) model. In the in-vitro study degranulated mesenteric cells were grouped into negative control (compound 48/80 treated), positive control (Disodium cromoglycate + 48/80 treated) and 3 test groups (EEQI 10 μg/ml + 48/80 treated, EEQI 50 μg/ml + 48/80 treated and EEQI 100 μg/ml + 48/80 treated). The number of degranulated mast cells was counted and compared within the different treatment groups. In the in-vivo study, the rats were first grouped into negative control (vehicle only), positive control (Disodium cromoglycate) and 2 test groups (EEQI: 100 and 200 mg/kilogram). The animals were pretreated for 12 days. On the 12th day, all the rats were immunized with serum anti-ovalbumin (obtained from an already sensitized rat) by the intradermal route. After 24 h of serum injection, Evans blue dye containing oval albumin was administered intravenously in all groups. Three days later, the rats were taken down for the severity of the anaphylactic reactions.Result:EEQI significantly attenuates mast cell degranulation and maintains cell intactness as compared to control (P &lt; 0.001). It was set up to support the degree of anaphylaxis as compared to the control group (P &lt; 0.001).Conclusion:The outcomes of the work revealed the preventive effect of Quisqualis indica Linn. against allergic manifestations.

Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India.

BackgroundZyCoV-D is a DNA vaccine candidate, which comprises a plasmid DNA carrying spike-S gene of SARS-CoV-2 virus along with gene coding for signal peptide. The spike(S) region includes the receptor-binding domain (RBD), which binds to the human angiotensin converting Enzyme (ACE)-2 receptor and mediates the entry of virus inside the cell.MethodsWe conducted a single-center, open-label, non-randomized, Phase 1 trial in India between July 2020 and October 2020. Healthy adults aged between 18 and 55 years were sequentially enrolled and allocated to one of four treatment arms in a dose escalation manner. Three doses of vaccine were administered 28 days apart and each subject was followed up for 28 days post third dose to evaluate safety and immunogenicity.FindingsOut of 126 individuals screened for eligibility. Forty-eight subjects (mean age 34·9 years) were enrolled and vaccinated in the Phase 1 study Overall, 12/48 (25%) subjects reported at least one AE (i.e. combined solicited and unsolicited) during the study. There were no deaths or serious adverse events reported in Phase 1 of the study. The proportion of subjects who seroconverted based on IgG titers on day 84 was 4/11 (36·36%), 4/12 (33·33%), 10/10 (100·00%) and 8/10 (80·00%) in the treatment Arm 1 (1 mg: Needle), Arm 2 (1 mg: NFIS), Arm 3 (2 mg: Needle) and Arm 4 (2 mg: NFIS), respectively.InterpretationZyCoV-D vaccine is found to be safe, well-tolerated and immunogenic in the Phase 1 trial. Our findings suggest that the DNA vaccine warrants further investigation.

Uso do Sapajus apella na padronização de modelo experimental para Schistosoma mansoni em primatas neotropicais

ABSTRACT OBJECTIVES: To establish and evaluate an experimental model with non-human neotropical primates Sapajus apella to verify more effective diagnostic methods in the detection of schistosomiasis, supporting new studies that help in the cure and control of this disease. MATERIALS AND METHODS: Six adult primates of the Sapajus apella species were used, randomly distributed in two experimental groups of equal number. Of these, three animals were infected intradermally and three transcutaneously, with suspension of cercariae obtained from naturally infected Biomphalaria glabrata snails. To monitor the infection, urine samples were collected via probe or direct puncture, with the anesthetized animal, and stool samples were collected directly from the cages. The urine samples were examined by the rapid urine test (point-of-care cathodic circulating antigen - POC-CCA) and the stool samples by tests of spontaneous stool sedimentation (HPJ) and Kato-Katz. RESULTS: The use of transcutaneous and intradermal routes resulted in the infection of two of the three animals evaluated (66.6%) in each experimental group. The POC-CCA test was the first to detect positives (21st day), followed by HPJ (35th day), and Kato-Katz (42nd day) tests. CONCLUSION: The model analyzed is viable for reproduction in different studies on schistosomiasis mansoni, as the animals responded satisfactorily to the infection in both routes used, making it possible to verify the practicality of the intradermal route when compared to the transcutaneous one.

The Route of Administration of Rabies Vaccines: Comparing the Data

Cell culture rabies vaccines were initially licensed in the 1980s and are essential in the prevention of human rabies. The first post-exposure prophylaxis (PEP) vaccination regimen recommended by the World Health Organization (WHO) was administered intramuscularly over a lengthy three-month period. In efforts to reduce the cost of PEP without impinging on safety, additional research on two strategies was encouraged by the WHO including the development of less expensive production methods for CCVs and the administration of reduced volumes of CCVs via the intradermal (ID) route. Numerous clinical trials have provided sufficient data to support a reduction in the number of doses, a shorter timeline required for PEP, and the approval of the intradermal route of administration for PEP and pre-exposure prophylaxis (PreP). However, the plethora of data that have been published since the development of CCVs can be overwhelming for public health officials wishing to review and make a decision as to the most appropriate PEP and PreP regimen for their region. In this review, we examine three critical benchmarks that can serve as guidance for health officials when reviewing data to implement new PEP and PreP regimens for their region including: evidence of immunogenicity after vaccination; proof of efficacy against development of disease; and confirmation that the regimen being considered elicits a rapid anamnestic response after booster vaccination.

Burden of illness of dog-mediated rabies in India: A systematic review

IntroductionIndia accounts for 35% of global burden of rabies. This systematic review attempts to measure the burden of illness of dog bites and dog-mediated rabies in India. MethodsA systematic literature search was conducted on MEDLINE, EMBASE, Cochrane Central, PROQUEST, Sodhganga and Google Scholar. Two independent reviewers screened titles and abstracts and included full texts as per inclusion criteria. Critical appraisal of included studies was conducted using appropriate checklists. Data was extracted using standardized data extraction tools, analyzed and reported in narrative summary and tabular formats. Results35 studies were included for narrative synthesis after screening for inclusion criteria. The annual crude dog bite incidence was reported between 0.26% and 2.5% with stray dogs as main biting animal. The bites were mainly reported in males, between age group 10–40 years, individuals belonging to low socio-economic status and people working in fields. The annual economic and humanistic burden is estimated to be 2.85 million USD and 1.3 million DALYs respectively. Use of intradermal route of vaccination and equine rabies immunoglobulins has been reported to save cost and resources over use of intramuscular route of vaccination and human rabies immunoglobulins. ConclusionThe review highlighted the burden of disease at local, regional and national level. There has been dearth of studies reporting economic and humanistic burden at national level. Systematic review registrationPROSPERO ID: CRD42020213261.

Immunogenic potential of DNA vaccine candidate, ZyCoV-D against SARS-CoV-2 in animal models

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially originated in China in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. Huge efforts were undertaken to bring the COVID-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. We developed a candidate vaccine ZyCoV-D comprising of a DNA plasmid vector carrying the gene encoding the spike protein (S) of the SARS-CoV-2 virus. The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme (ACE-2) receptor. The DNA plasmid construct was transformed into E. coli cells for large scale production. The immunogenicity potential of the plasmid DNA has been evaluated in mice, guinea pig, and rabbit models by intradermal route at 25, 100 and 500 µg dose. Based on the animal studies proof-of-concept has been established and preclinical toxicology (PCT) studies were conducted in rat and rabbit model. Preliminary animal study demonstrates that the candidate DNA vaccine induces antibody response including neutralizing antibodies against SARS-CoV-2 and also elicited Th-1 response as evidenced by elevated IFN-γ levels.

Immunological Evaluation of Influence of Dose and Route of Immunization with FMD Serotype ‘A’ Vaccine in Guinea Pigs

A study has been conducted to measure the immunization efficacy of route of inoculation between intra dermal (ID) and intra muscular (IM) in guinea pigs, using FMD vaccines. Three different vaccine formulations of varying concentrations containing full dose, 1/5th dose, 1/10th dose were prepared and injected either intra muscularly or intra dermal to six different groups of guinea pigs. At 30th day post vaccination, all the animals were challenged. Efficacy of route was defined in terms of serum neutralizing antibodies, IgG1 and IgG2 isotype response and challenge studies. When compared with guinea pigs that were intramuscularly vaccinated with a full dose vaccine, guinea pigs vaccinated intra dermal with 1/5th dose of the vaccine were 60% protected against clinical disease. Thus, we conclude that ID route is a good alternative for IM route, as ID route has shown to induce a very efficient immunological response against FMD. Moreover, the dose required by the ID route is lower compared to the IM route with an added benefit of reduced requirement of antigen and costs per dose of FMD vaccine.

Does the use of Dermojet affect the concentration of platelet‐rich plasma? An in vitro experimental investigation

Needle-free injection systems with high jet pressure have been used for seven decades for drug or vaccine administration via intradermal, subcutaneous, and intramuscular routes. These systems are used for the application of mesotherapy drugs in plastic surgery and dermatology. Platelet-rich plasma (PRP) tissue regeneration is applied intradermally by a needle for different indications, such as wound healing and scar revision. To prevent complaints such as pain, erythema, and ecchymosis by patients during this application, PRP was applied using Dermojet, a jet injector system with a spring-loaded system. In this study, after measuring the average platelet count in PRP preparations obtained from 18 volunteers, a 2.5cc PRP shot into an empty tube was performed with Dermojet. The mean platelet count was measured in a homogenized tube. The same procedures were performed for platelet-poor plasma (PPP). The platelet loss rates for PRP and PPP were compared. In addition, the amount of PRP in each shot of the Dermojet was calculated. When PRP and PPP were applied using the Dermojet, platelet loss was 8.41% and 8.33%, respectively. The difference in the number of platelets formed in PRP and PPP when applied with Dermojet was not statistically significant. PRP application with needle-free injection systems, such as Dermojet, may be an alternative because of patient comfort and the negligible platelet loss compared with the PRP application with the standard needle injection.

Efficacy and safety of tranexamic acid in the treatment of adult melasma: An updated meta-analysis of randomized controlled trials.

Tranexamic acid (TXA) is a novel treatment option for melasma; however, no consensus exists on its use. This study evaluates the efficacy and safety of TXA for melasma. A comprehensive literature review was conducted to search for randomized controlled trials comparing TXA alone, TXA as adjuvant to routine treatment and placebo. Changes in the Melasma Area Severity Index (MASI)/modified MASI (mMASI) between pre- and post-treatment and between a certain melasma treatment and TXA were the primary outcomes. Twenty-four trials comparing oral, topical or intradermal TXA with routine treatment were included in the meta-analysis. The change in MASI/mMASI scores at 4 (MD, 3.58; 95% confidence interval (CI), 2.15-5.01), 8 (MD, 5.08; 95% CI, 3.34-6.81), 12 (MD, 4.89; 95% CI, 3.80-5.97) and 16 (MD, 6.55; 95% CI, 2.62-10.48) weeks after treatment was all less than the baseline scores, regardless of the delivery route. The reduction in the MASI/mMASI scores between TXA adjuvant and routine treatment at 4 (MD, -0.43; 95% CI, -0.79 to -0.08), 8 (MD, -0.81; 95% CI, -1.09 to -0.54), 12 (MD, -1.10; 95% CI, -1.78 to -0.43) and 16 (MD, -1.12; 95% CI, -1.51 to -0.74) weeks was significant. However, the superiority of TXA was not detected when the topical or intradermal route was adopted. No serious adverse events occurred with the use of TXA. These results suggest that oral TXA is an available, effective and safe alternative treatment for melasma.

Comparative immunogenicity analysis of intradermal versus intramuscular administration of SARS-CoV-2 RBD epitope peptide-based immunogen In vivo

COVID-19 pandemic has caused severe disruption of global health and devastated the socio-economic conditions all over the world. The disease is caused by SARS-CoV-2 virus that belongs to the family of Coronaviruses which are known to cause a wide spectrum of diseases both in humans and animals. One of the characteristic features of the SARS-CoV-2 virus is the high reproductive rate (R0) that results in high transmissibility of the virus among humans. Vaccines are the best option to prevent and control this disease. Though, the traditional intramuscular (IM) route of vaccine administration is one of the effective methods for induction of antibody response, a needle-free self-administrative intradermal (ID) immunization will be easier for SARS-CoV-2 infection containment, as vaccine administration method will limit human contacts. Here, we have assessed the humoral and cellular responses of a RBD-based peptide immunogen when administered intradermally in BALB/c mice and side-by-side compared with the intramuscular immunization route. The results demonstrate that ID vaccination is well tolerated and triggered a significant magnitude of humoral antibody responses as similar to IM vaccination. Additionally, the ID immunization resulted in higher production of IFN-γ and IL-2 suggesting superior cellular response as compared to IM route. Overall, our data indicates immunization through ID route provides a promising alternative approach for the development of self-administrative SARS-CoV-2 vaccine candidates.

Intradermal Vaccination: A Potential Tool in the Battle Against the COVID-19 Pandemic?

This narrative review is the final output of an initiative of the SIM (Italian Society of Mesotherapy). A narrative review of scientific literature on the efficacy of fractional intradermal vaccination in comparison with full doses has been conducted for the following pathogens: influenza virus, rabies virus, poliovirus (PV), hepatitis B virus (HBV), hepatitis A virus (HAV), diphtheria-tetanus-pertussis bacterias (DTP), human papillomavirus (HPV), Japanese encephalitis virus (JE), meningococcus, varicella zoster virus (VZV) and yellow fever virus. The findings suggest that the use of the intradermal route represents a valid strategy in terms of efficacy and efficiency for influenza, rabies and HBV vaccines. Some systematic reviews on influenza vaccines suggest the absence of a substantial difference between immunogenicity induced by a fractional ID dose of up to 20% and the IM dose in healthy adults, elderly, immunocompromised patients and children. Clinical studies of remaining vaccines against other pathogens (HAV, DTP bacterias, JE, meningococcal disease, VZV, and yellow fever virus) are scarce, but promising. In the context of a COVID-19 vaccine shortage, countries should investigate if a fractional dosing scheme may help to save doses and achieve herd immunity quickly. SIM urges the scientific community and health authorities to investigate the potentiality of fractionate intradermal administration in anti-COVID-19 vaccination.

Vaccine Inoculation Route Modulates Early Immunity and Consequently Antigen-Specific Immune Response.

Vaccination is one of the most efficient public healthcare measures to fight infectious diseases. Nevertheless, the immune mechanisms induced in vivo by vaccination are still unclear. The route of administration, an important vaccination parameter, can substantially modify the quality of the response. How the route of administration affects the generation and profile of immune responses is of major interest. Here, we aimed to extensively characterize the profiles of the innate and adaptive response to vaccination induced after intradermal, subcutaneous, or intramuscular administration with a modified vaccinia virus Ankara model vaccine in non-human primates. The adaptive response following subcutaneous immunization was clearly different from that following intradermal or intramuscular immunization. The subcutaneous route induced a higher level of neutralizing antibodies than the intradermal and intramuscular vaccination routes. In contrast, polyfunctional CD8+ T-cell responses were preferentially induced after intradermal or intramuscular injection. We observed the same dichotomy when analyzing the early molecular and cellular immune events, highlighting the recruitment of cell populations, such as CD8+ T lymphocytes and myeloid-derived suppressive cells, and the activation of key immunomodulatory gene pathways. These results demonstrate that the quality of the vaccine response induced by an attenuated vaccine is shaped by early and subtle modifications of the innate immune response. In this immunization context, the route of administration must be tailored to the desired type of protective immune response. This will be achieved through systems vaccinology and mathematical modeling, which will be critical for predicting the efficacy of the vaccination route for personalized medicine.

Assessment of Maternal Immunity Against LSD in Calves Born to Cows Immunized with Sheep Pox Vaccine at Different Time of Gestation Period

Lumpy skin disease (LSD) is a poxvirus disease of cattle characterized by fever, nodules on the skin, mucous membranes and internal organs, emaciation, enlarged lymph nodes, edema of the skin, and sometimes death. Vaccination of cattle is the most effective option for controlling the spread of lumpy skin disease. All the vaccines used to prevent LSD are currently based on live attenuated viruses. Two types of vaccines against LSD are commercially available; lumpy skin disease vaccine and sheep pox vaccine with the latter is commonly used, but their ability to induce passive immunity is poorly known. Here, we evaluated the passive immunity transferred from dams immunized with sheep pox vaccine to calves. Pregnant cattle were injected with living attenuated sheep pox vaccine Romanian strain via intradermal route. Clinical conditions were monitored throughout the study. The humoral immune response was evaluated in dam and in serum samples collected from newborn calves. The results indicated that sheep pox vaccine vaccines are safe and produce a good humoral immune response in pregnant cattle. Moreover, results showed that, in calf serum, passive immunity persists until three months of age.