Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac

Background Currently, booster dose is needed after 2 doses of inactivated COVID-19 vaccine. With limited resource and shortage of COVID-19 vaccine, intradermal(ID) administration might be a potential dose-sparing strategy. Objective To determine antibody 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(1x1010 viral particles,0.1ml). Antibody responses were evaluated by surrogate virus neutralization test(sVNT) against wild type and delta variant and anti-spike-receptor-binding-domain immunoglobulin G(anti-S-RBD IgG) at prior, day14 or 28, and day90 post booster. Solicited reactogenicity was collected during 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(IQR) age of 46(41-52) years participated. At baseline, geometric means(GMs) of sVNT against delta strain prior to booster were 22.4%inhibition(95%CI 18.7-26.9) and of anti-S-RBD IgG were 109.3(95.4-125.1)BAU/ml. GMs of sVNT against delta strain were 92.9%inhibition(95%CI 87.7-98.3) at day14 and 73.1%inhibition(66.7-80.2) at day90 post ID booster. The differences of proportion of participants with sVNT to 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(95%CI1770.9-2343.2) at day14 and 744.6(650.1-852.9) BAU/ml 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). Only 18% reported feverish, compared with 37% of IM(p=0.003). Common reactogenicity was erythema(55%) at injection site 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.

Preclinical Immunological Evaluation of an Intradermally Administered Heterologous Vaccine Against SARS-CoV-2 Variants

The recent emergence of new variants in the COVID-19 pandemic has led to new requirements for vaccines, with a focus on the capacity of vaccines to elicit high levels of neutralizing antibodies with specific recognition of S antigen variants based on the characterized vaccines licensed for use. A new strategy involving a heterologous vaccine composed of one or two doses of inactivated vaccine and a boost with the S1 protein with mutations (K-S) administered via the intradermal route was designed in this work and was found to improve immune efficacy by increasing neutralizing antibody titers and promoting specific T cell responses against 5 variants of the RBD peptide. A viral challenge test with the B.1.617.2 (Delta) variant confirmed that the both schedules of “1+1” and “2+1” administration ensured a clinical protective effect against this strain. All of these results not only suggested the feasibility of our strategy for protecting against new variants but also provided a technical pathway to enhance the anamnestic immune response in the immunized population.

Evaluating Efficacy and Safety of Intradermal Delivery of Vaccines through Microneedle(s) in Animals: Systematic Review Protocol (Preprint)

BACKGROUND Microneedles are defined as micron-sized projections that create microscopic holes to the skin on application so that drug molecules can penetrate across the outer layers of the skin into the dermis or deeper. Skin is a natural barrier for defense against invading pathogens. Additionally, the dermis possesses dendritic cells that are efficient for antigen presentation and initiating the cascade of immunogenic responses leading to antibody production. Therefore, intradermal delivery of vaccine antigens could be a safe and less invasive alternative for vaccine delivery compared with conventional intramuscular injection. OBJECTIVE We intend to undertake a systematic review of the literature to evaluate the efficacy and safety of intradermal delivery of vaccines using microneedles in animal models. METHODS In this systematic review, we will consider all study designs evaluating the safety and/or efficacy of intradermal delivery of vaccines using microneedles in animal models. Our search strategy will include free text terms and controlled vocabulary for, “microneedle”, “vaccine”, and “intradermal”. We will search literature through PubMed, Embase, Cochrane, and OpenGrey, and we will not have language or date limits. Two review authors will independently select eligible studies and assess the risk of bias using the SYRCLE’s tool particularly for controlled studies and OHAT Risk of Bias Rating Tool for case studies, case-control studies, non-randomized studies, and cohort studies, and CAMARADES checklist to appraise the quality of the included studies. We will report structured summaries of the included studies and, if possible, conduct meta-analyses. The primary outcome to be measured is the efficacy of vaccine delivered through an intradermal route using microneedle(s) such as parameters of immunogenicity (for example antibody levels), sero-efficacy (for example sero-conversion), protective efficacy, etc. Secondary outcomes would include the safety of vaccines delivered through the intradermal route. This could include parameters to identify and/or quantify the timing and nature of local reactions, bleeding, systemic reactions, and death. Pain response during vaccination delivered through the intradermal route will also be evaluated. RESULTS This is a protocol for a systematic review; therefore, results are not available. CONCLUSIONS This is the first systematic review protocol aiming to assess the evidence on the efficacy and safety of intradermal delivery of vaccines using microneedles in various animal models. The findings will inform the safety and efficacy of intradermal delivery of vaccines in animal models, with the overall goal of considering the method for human vaccination as well. The results of this study will be published in a peer-reviewed journal. CLINICALTRIAL PROSPERO CRD42021236625

29-kDa: A Potential Candidate for Anti-Tick Vaccine Antigen Source as Immunogenic and Stage Reactive Targeting Hard-Bodied Hyalomma Ticks Ixodidae

The objective of present study is to develop a vaccine against Hyalomma hard-bodied tick and to analyze relevant experimental data on immunized indigenous horse breed Morna. Montanide (ISA-50) adjuvant-based vaccine induced significantly (pandlt;0.02) higher antibody titre through intradermal route with 99.98% vaccine efficacy. Humoral response was determined though indirect ELISA; where peak level of serum antibody was recorded after six weeks interval of post-immunization. Most of hematology and biochemical parameters remained consistent to normal reference values. Our report also indicates a significant percentage decline in the numbers of engorged ticks, eggs mass, eggs number and increased tick rejection. The animal travel history can promote tick burden and is a potential risk factor. Based on biological and hematological parameters, it is possible to conclude that 29-kDa antigen can be used as an effective antigen vaccine candidate to control tick infestation detected through humoral response.

Intradermal Synthetic DNA Vaccination Generates Leishmania-Specific T Cells in the Skin and Protection against Leishmania major

ABSTRACT Vaccination remains one of the greatest medical breakthroughs in human history and has resulted in the near eradication of many formerly lethal diseases in many countries, including the complete eradication of smallpox. However, there remain a number of diseases for which there are no or only partially effective vaccines. There are numerous hurdles in vaccine development, of which knowing the appropriate immune response to target is one of them. Recently, tissue-resident T cells have been shown to mediate high levels of protection for several infections, although the best way to induce these cells is still unclear. Here we compare the ability to generate skin-resident T cells in sites distant from the immunization site following intramuscular and intradermal injection using optimized synthetic DNA vaccines. We found that mice immunized intradermally with a synthetic consensus DNA HIV envelope vaccine by electroporation (EP) are better able to maintain durable antigen-specific cellular responses in the skin than mice immunized by the intramuscular route. We extended these studies by delivering a synthetic DNA vaccine encoding Leishmania glycosomal phosphoenolpyruvate carboxykinase (PEPCK) by EP and again found that the intradermal route was superior to the intramuscular route for generating skin-resident PEPCK-specific T cells. We observed that when challenged with Leishmania major parasites, mice immunized intradermally exhibited significant protection, while mice immunized intramuscularly did not. The protection seen in intradermally vaccinated mice supports the viability of this platform not only to generate skin-resident T cells but also to promote durable protective immune responses at relevant tissue sites.

INTRADERMAL ANTIRABIES VACCINATION: A COSTEFFECTIVE METHOD

Background: Compliance to post-exposure vaccination is crucial to achieve optimum level of antibody titers. The present study was planned to assess the cost effectiveness of 4 dose intradermal regimen over 5 dose intramuscular regimen. The objective of present study is to reveal cost effectiveness of intradermal regimen over intramuscular PEP regimenMethods: Hospital record based study. Patients who attended antirabies clinic from Jan 2010 to Dec 2010 were studied. 2051 patients who were given Inj. PCECV by intradermal route formed the study group. Pearson’s Chi square test was used as a test of significance.Results: 2051 patients were studied.1741 (84.9%) patients were male.1907 (92.9%) were dog bites. 1277(62.3%) were stray dog bites. 1516 (58.0%) were class III dog bites.1313 (68.2%) were non-observable dog bites.1711 (88.7%) were provoked dog bites. Most common site of dog bite was over the lower limb i.e.1350 (70.2%).1255 (65.3%) patients completed the 4 dose regimen. This is in stark contrast to previous evidence from our centre in which a compliance of 40.2% to the intramuscular regimen was evident. (Pearson X2 = 180.94, df= 1, p< 0.0001). Cost effectiveness favored intradermal regimen over intramuscular regimen.Conclusions: It was observed intradermal regimen had more cost effectiveness compared to intramuscular regimen.