UPAYA PELAKSANAAN DAN PEMANTAUAN KEJADIAN KIPI PADA PELAKSANAAN VAKSINASI COVID-19

Post-Immunization Adverse Events (AEFI) are medical events that occur after immunization, and need attention. given counseling and IEC media about COVID-19 prevention and COVID-19 vaccination. The purpose of this PKM activity is to provide health promotion services through monitoring and education related to the anticipation of the Covid 19 vaccine AEFI. The benefits of the PKM activity are that vaccination participants are protected from AEFIs and the PKM TEAM contributes to caring for others in the health sector, especially the implementation of promotive and preventive efforts. The short-term target of the PKM activity is the Covid-19 vaccination participants, namely the elderly to avoid AEFIs and the long-term target is to improve the health status of the Covid-19 vaccination participants and assist the "Jakarta Responding Corona" program. March 27, 2021. The number of participants who can be vaccinated is 156 people consisting of 153 elderly and 2 health workers and 1 ASN. Of the 156 participants who were vaccinated, none experienced a post-immunization follow-up event (AEFI).Kejadian Ikutan Pasca Imunisasi (KIPI) merupakan kejadian medik yang terjadi setelah dilakukan imunisasi, dan perlu mendapat perhatian sesuai dengan alur pelayanan vaksinasi COVID-19 yaitu pada meja pelayanan vaksin nomor 4. Tenaga medis mempersilakan penerima vaksinasi untuk menunggu selama 30 menit di ruang observasi dan diberikan penyuluhan tentang KIE, pencegahan COVID-19 dan vaksinasi COVID-19. Tujuan Kegiatan PKM ini adalah memberikan pelayanan promosi kesehatan melalui pemantauan dan edukasi terkait antisipasi KIPI yang dapat timbul paska vaksin Covid 19. Manfaat dari kegiatan PKM adalah peserta vaksinasi terhindar dari KIPI serta TIM PKM berkontribusi dalam kegiatan kepedulian bagi sesama di bidang kesehatan terutama penerapan pelaksanaan upaya promotif dan preventif. Target jangka pendek kegiatan PKM adalah peserta vaksinasi Covid-19 yaitu lansia terhindar KIPI dan target jangka panjang adalah meningkatkan derajat kesehatan peserta vaksinasi Covid-19 dan membantu program “Jakarta Tanggap Corona".Pelaksanaan vaksinasi dalam upaya pencegahan Covid-19 dilakukan pada tanggal 24 – 27 Maret 2021. Jumlah peserta yang dapat divaksinasi sebanyak156 orang terdiri dari 153 lansia dan 2 tenaga kesehatan dan 1 ASN. Dari 156 peserta yang divaksin, tidak ada yang mengalami kejadian ikutan paska imunisasi (KIPI).

Distinct neutralizing kinetics and magnitudes elicited by different SARS-CoV-2 variant spikes

The rapid evolution of SARS-CoV-2 mandates a better understanding of cross-protection between variants after vaccination or infection, but studies directly evaluating such cross-protection are lacking. Here we report that immunization with different variant spikes elicits distinct neutralizing kinetics and magnitudes against other SARS-CoV-2 variants. After immunizing hamsters with wild-type or mutant SARS-CoV-2 bearing variant spikes from Alpha, Beta, Gamma, or Epsilon, the animals developed faster and greater neutralization activities against homologous SARS-CoV-2 variants than heterologous variants, including Delta. The rank of neutralizing titers against different heterologous variants varied, depending on the immunized variant spikes. The differences in neutralizing titers between homologous and heterologous variants were as large as 62-, 15-, and 9.7-fold at days 14, 28, and 45 post-immunization, respectively. Nevertheless, all immunized hamsters were protected from challenges with all SARS-CoV-2 variants, including those exhibiting the lowest neutralizing antibody titers. The results provide insights into the COVID-19 vaccine booster strategies.

Choroid Plexus-Selective Inactivation of Adenosine A2A Receptors Protects Against T Cell Infiltration And Experimental Autoimmune Encephalomyelitis

Background: Multiple sclerosis (MS) is one of the most common autoimmune disorders characterized by the infiltration of immune cells into the brain and demyelination. The unwanted immunosuppressive side effect of therapeutically successful natalizumab led us to focus on choroid plexus (CP), a key site for the first wave of immune cell infiltration in experimental autoimmune encephalomyelitis (EAE), for the control of immune cells trafficking. Adenosine A2A receptor (A2AR) is emerging as a potential pharmacological target to control EAE pathogenesis; however, the cellular basis for the A2AR-mediated protection remains undetermined. Methods: In EAE model, we assessed A2AR expression and leukocyte trafficking determinants in CP by immunohistochemistry and qPCR analyses. We determined the effect of the A2AR antagonist KW6002 treatment at days 8-12 or 8-14 post-immunization on T cell infiltration across CP and EAE pathology. We determined the critical role of the CP-A2AR on T cell infiltration and EAE pathology by focal knockdown the CP-A2AR with intracerebroventricular injection of CRE-TAT recombinase into the A2ARflox/flox mice. In cultured CP epithelium, we also evaluated the effect of overexpression of A2ARs or the A2AR agonist CGS21680 treatment on CP permeability and lymphocytes migration. Results: We found the specific upregulation of A2AR in CP in association with enhanced CP gateway activity peaked at day 12 post-immunization in EAE mice. Furthermore, the KW6002 treatment at days 8-12 or 8-14 post-immunization reduced T-cell trafficking across CP and attenuated EAE pathology. Importantly, focal CP-A2AR knockdown attenuated pathogenic infiltration of Th17+ cells across CP via inhibiting CCR6-CCL20 axis through NFκB / STAT3 pathway and protected against EAE pathology. Lastly, activation of A2AR in cultured epithelium by A2AR overexpression or CGS21680 treatment increased the permeability of CP epithelium and facilitated lymphocytes migration. Conclusion: These findings define the CP niche as one of the primary sites of A2AR action whereby A2AR antagonists confer protection against EAE pathology. Thus, pharmacological targeting of the CP-A2AR represents a novel therapeutic strategy for MS by controlling immune cell trafficking across CP.

Comparable neutralization of SARS-CoV-2 Delta AY.1 and Delta in individuals sera vaccinated with BBV152

The recent emergence of the SARS-CoV-2 Variant of Concern B.1.617.2 (Delta) variant and its high transmissibility has led to the second wave in India. BBV152 a whole-virion inactivated SARS-CoV-2 vaccine used for mass immunization in India, showed a 65.2% protection against the Delta variant in a double-blind, randomized, multicentre, phase 3 clinical trial. Subsequently, Delta has been further mutated to Delta AY.1, AY.2, and AY.3. Of these, AY.1 variant was first detected in India in April 2021 and subsequently from twenty other countries as well. Here, we have evaluated the IgG antibody titer and neutralizing potential of sera of COVID-19 naive individuals full doses of BBV152 vaccine, COVID-19 recovered cases with full dose vaccines and breakthrough cases post-immunization BBV152 vaccines against Delta, Delta AY.1 and B.1.617.3. A reduction in neutralizing activity was observed with the COVID-19 naive individuals full vaccinated (1.3, 1.5, 1.9-fold), COVID-19 recovered cases with full BBV152 immunization (2.5, 3.5, 3.8-fold) and breakthrough cases post-immunization (1.9, 2.8, 3.5-fold) against Delta, Delta AY.1 and B.1.617.3 respectively compared to B.1 variant. A minor reduction was observed in the neutralizing antibody titer in COVID- 19 recovered cases full BBV152 vaccinated and post immunized infected cases compared to COVID-19 naive vaccinated individuals. However, with the observed high titers, the sera of individuals belonging to all the aforementioned groups they would still neutralize the Delta, Delta AY.1 and B.1.617.3 variants effectively.

Immunogenicity and efficacy of live-attenuated Salmonella Typhi murium vaccine candidate CVD 1926 in a rhesus macaque model of gastroenteritis

Salmonella Typhi murium are a common cause of food-borne gastroenteritis, and a less frequent but important cause of invasive disease, especially in developing countries. In our previous work, we showed that a live-attenuated S. Typhi murium vaccine (CVD 1921) was safe and immunogenic in rhesus macaques, although shed for an unacceptably long period (10 days) post-immunization. Consequently, we engineered a new strain, CVD 1926, which was shown to be safe and immunogenic in mice, as well as less reactogenic in mice and human cell-derived organoids than CVD 1921. In this study, we assessed reactogenicity and efficacy of CVD 1926 in rhesus macaques. Animals were given two doses of either CVD 1926 or saline perorally. The vaccine was well-tolerated, with shedding in stool limited to a mean of 5 days. All CVD 1926 immunized animals made both a serological and a T cell response to vaccination. At four weeks post-immunization, animals were challenged with wild-type S. Typhi murium I77. Unvaccinated (saline) animals had severe diarrhea, with two animals succumbing to infection. Animals receiving CVD 1926 were largely protected, with only one animal having moderate diarrhea. Vaccine efficacy in this gastroenteritis model was 80%. S. Typhi murium vaccine strain CVD 1926 was safe and effective in rhesus macaques and shed for a shorter period than other previously tested live-attenuated vaccine strains. This strain could be combined with other live-attenuated Salmonella vaccine strains to create a pan- Salmonella vaccine.

OP0042 BLOCKING OF CD103+ TISSUE RESIDENT MEMORY T CELLS (TRM) AS A THERAPEUTIC STRATEGY IN SJOGREN’S SYNDROME

Background:Tissue-resident memory T cells (TRM), are a recently identified T cells population featuring tissue localization and expression of markers of tissue homing, CD69 and CD103. Recently, the expansion of CD8+ TRMs and their involvement in the sialadenitis was described in a murine model of SS. However, CD4+ and CD8+ TRM’s functional relevance in pSS is still not fully understood, and the TRM therapeutic targeting unexplored.Objectives:The study aimed to address the role of CD4+ and CD8+ TRMs in the pathogenesis of pSS and to explore the therapeutic targeting of the tissue residency marker of TRM CD103.Methods:An animal model of experimental (ESS) obtained by immunization of female C57BL/6 mice (n=10) with salivary glands (SG) protein extract and Freund’s complete adjuvant used to investigate the dynamic of infiltration of SG by CD4+ and CD8+ TRMs, their frequency, and the impact of CD103 blockade. For the therapeutic intervention, at 10-weeks post-immunization, the salivary gland was cannulated via Wharton’s duct, and an anti-CD103 neutralizing antibody or vehicle-injected. The mice’s saliva flow rate was assessed, and SGs were analyzed by Flow-cytometry and immunohistochemistry (IHC).The frequency and localization of TRMs was analyzed in minor SG of sicca syndrome (nSS) and pSS patients (n=39) by flow cytometry and IHC. The expression of genes involved in the tissue retention of TRMs was assessed in SG by RT-PCR.Results:Upon the ESS progression, a significant progressive increase in CD45+CD103+ cells frequency was observed from 5wk to 20wk post-immunization (p<0.001), where the CD8+ were the most abundant, followed by CD4+. Consistently, CD103+CD8+ T cells were detected within the lymphocytic infiltration of SG from ESS mice. Sorted purified SG CD10+CD3+CD8+ T cells showed higher Granzyme B, TNF-alpha expression compared to CD103-CD3+CD8+ at both mRNA and protein levels. Notably, ESS mice treated with anti-CD103 showed improvement in salivary function (p<0.05) and reduced lymphocytic infiltrations measured as focus score (FS) (p<0.01) and area-fraction (p<0.01). Consistently, anti-CD103 treatment consistently reduced CD103+ cells and IFN-gamma+, Granzyme B+, and TNFa+ CD8+ cells. We next performed phenotypic analysis of CD45+CD103+ immune cells in the SG of pSS patients observing an increase in both with CD8+CD103+CD69+ and CD4+CD103+CD69+ (p<0.05). Finally, IHC showed that the expansion of TRMs in pSS salivary glands was accompanied by a down-regulation of E-cadherin glandular expression and their migration outside the epithelium in the context of inflammatory infiltrates. SG of patients with pSS showed a significant up-regulation of BLIMP1, KFL-2, and S1PR1 and down-regulation of ITGB2. CXCL9 and CXCL10, and IL-15 involved in the tissue recruitment and long-term survival of TRMs were significantly modulated in pSS salivary glands.Conclusion:TRM are expanded and activated in the SG of pSS and ESS, participating in the organization of tissue inflammation. Although the mechanisms behind this expansion are still not fully understood, CD103 could be a valuable novel therapeutic target to prevent lymphocytic infiltrations and glandular destruction in Sjogren syndrome.Disclosure of Interests:None declared

Protective Efficacy of Chitosan Coupled Johne’s Disease Vaccine

Background: Johne’s disease (JD) is a chronic, economically important disease of domestic ruminants. Continuous efforts are being made to develop a potent vaccine for JD which confer a longer immunity. The present study was aimed at developing chitosan nanoparticles coupled JD vaccine and assess its efficacy. Methods: Potency of a heat killed, chitosan nanoparticle coupled JD vaccine developed with an Indian isolate of Mycobacterium avium subsp paratuberculosis (MAP) was tested in 107 goats. Pre and post immunization blood samples were collected at different time points and peripheral blood mononuclear cells were used for assessing IFN-γ, IL-2, IL-10 and IL-12 gene expressions. Immunized animals were challenged with a field isolate of MAP and the immune response was assessed. Result: Immunized goats were safe with no untoward reactions. Cytokine gene expression studies indicated a good Th1 response during 3-14 wk post immunization. The initial Th1 response was followed by a good Th2 response with a better IL-10 response than the IFN-γ and IL-2 responses in vaccinated animals at 23 wk PI. Both Th1 and Th2 responses were significantly higher in immunized animals at 23 and 34 weeks post challenge indicating a protective immune response.

Role of African swine fever virus (ASFV) proteins EP153R and EP402R in reducing viral persistence and virulence from attenuated BeninΔDP148R

The limited knowledge on the role of many of the approximately 170 proteins encoded by African swine fever virus restricts progress towards vaccine development. In this study we investigated the effect of deleting combinations of different genes from a previously attenuated virus, BeninΔDP148R on: virus replication in macrophages, virus persistence and clinical signs post immunization, and induction of protection against challenge. Deletion of either EP402R or EP153R genes individually or in combination from BeninΔDP148R did not reduce virus replication in vitro. However, deletion of EP402R dramatically reduced viral persistence in vivo, whilst maintaining high levels of protection against challenge. The additional deletion of EP153R (BeninΔDP148RΔEP153RΔEP402R) further attenuated the virus and no viremia or clinical signs were observed post immunization. This was associated with decreased protection and detection of moderate levels of challenge virus in blood. Interestingly, the deletion of EP153R alone from BeninΔDP148R did not result in further virus attenuation and a slight increase in virus genome copies in blood was observed at different times post immunization when compared with BeninΔDP148R. These results show that EP402R and EP153R have a synergistic role in promoting viremia, however EP153R alone does not seem to have a major impact on virus levels in blood.

One dose of COVID-19 nanoparticle vaccine REVC-128 provides protection against SARS-CoV-2 challenge at two weeks post immunization

A COVID-19 vaccine with capability to induce early protection is needed to efficiently eliminate viral spread. Here, we demonstrate the development of a nanoparticle vaccine candidate, REVC-128, in which multiple trimeric spike ectodomain subunits with glycine (G) at position 614 were multimerized onto a nanoparticle. In-vitro characterization of this vaccine confirms its structural and antigenic integrity. In-vivo immunogenicity evaluation in mice indicates that a single dose of this vaccine induces potent serum neutralizing antibody titer at two weeks post immunization, which is significantly higher than titer induced by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by spike with and without nanoparticle presentation indicates that nanoparticle prefers the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for SARS-CoV-2 virus challenge was implemented at two weeks post a single dose of REVC-128 immunization. The results show that vaccination protects hamsters against SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage (lung and nares) for protected animals, compared with ~10% weight loss, higher viral loads and tissue damage in unprotected animals. Furthermore, the data show that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks. These findings, along with a long history of safety for protein vaccines, suggest that the REVC-128 is a safe, stable and efficacious single-shot vaccine candidate to induce the earliest protection against SARS-CoV-2 infection.