Malaria vaccine updates

 Table 1: List of malaria vaccines

Type of Vaccines	Name: Compositions	Beneficial / Limitations
Pre-erythrocytic vaccines	1.       RTS,S/AS01E ·         Adenovirus (Ad35) vectored circumsporozoite (CS) protein in prime boost with RTS,S/AS01E ·         Multiple epitope constructs (ME-TRAP); a pre-erythrocytic fusion antigen consisting of 17 B-cell, CD4+, CD8+ T cell epitopes of 6 Pf antigens fused to the T9/96 allele of TRAP (Thrombospondin related adhesion protein)	·         Only the vaccine in Phase 3 clinical trial ·         Low efficacy but decreases mortality
	2.       AdCh63/MVA ME-TRAP ·         Simian Adenovirus (Ad35) encoding ME-TRAP boosted with modified vaccinia virus Ankara (MVA)	·         Long lasting CD8+ T cell responses
	3.       Polyepitope DNA EP1300 ·         DNA vaccine includes multiple epitopes with linker sequences from four pre-erythrocytic antigens CS, SSP2/TRAP, liver stage antigen-1 (LSA-1) and Exported protein-1 (EP-1)	·         Immunogenicity is not enhanced in human as compared to animals
	4.       PfSPZ ·         Metabolically active non-replicating malaria sporozoite vaccine (Pf sporozoites prepared by thawing from liquid nitrogen)	·         Not protective but need to revised in terms of dose and route of administration
	5.       Genetically Attenuated sporozoites-GAS	·         Safe and immunogenic
	6.       FP9 CS/MVA CS ·         Attenuated fowl pox strain (FP9) expressing CS protein boosted with MVA coding CS protein	·         Didn’t boost the T-cell response
	7.       DNA CS/MVA CS ·         Plasmid DNA encoding CS protein replace fowl pox strain (FP9) boosted with MVA coding CS protein	·         Modest T-cell response
	8.       RTS,S/AS02 + MVA CS ·         Boosting RTS,S/AS02 with MVA encoding CS	·         Greater CMI response ·
	9.       CS DNA Immunization or VCL-2510 ·         Gene for full length CS protein in Plasmid DNA	·         No anti-CS antibodies
	10.   MUST DO5 ·         Multi-Stage DNA vaccine operation 5 antigens ·         5 antigens; CS, SSP2/TRAP, LSA-1, LSA-3 and EP-1 adjuvanted with GM-CSF (Granulocyte Macrophage colony stimulating factor)	·         No efficacy
	11.   DNA CS / RTS,S/AS02 ·         DNA vaccine VCL-2510 containing full length CS gene and adjuvanted with RTS,S/AS02	·         No significant improvement than using alone
	12.   RTS,S/AS02 TRAP ·         Combination of CS with TRAP	·         Improve efficacy
	13.   HepB Core Ag CS VLP ·         Also called ICC-1132 or Malariavax ·         Hepatis B core antigen modified to include B-cell and 2 CD4+ epitopes of CS protein	·         No efficacy to sporozoites
	14.   PfCS102 ·         Chemically synthesized Pf CS protein with C-terminus (Amino acids 282-383)	·         Don’t reduce parasitemia
	15.   FP9/MVA polyprotein ·         Prime Boosting with FP9 and MVA viruses with six antigens polyprotein (STARP, TRAP, LSA-1, LSA-3, Pfs16 and EP-1)	·         Low efficacy with sporozoite challenge
	16.   FMP011/AS01B ·         LAS-1 E. coli expressed evaluated with AS01B and AS02A	·         Associated with acute coronary syndrome
Blood Stage (Erythrocytic) vaccines	1.       AdCh63/MVA MSP-1 ·         Pf Merozoite Surface Protein-1 (MSP-1) expressed and boosted with AdCh63 and MVA vectors	·         Low IgG response
	2.       FMP010/AS01B ·         E. coli expressing FVO allele 42kD C terminus of MSP-1 and adjuvants AS01B	·         Good immunogenicity but inadequate clinical efficacy
	3.       FMP2.1/AS02A ·         FMP2.1, in which E. coli expressed Apical membrane antigen (AMA-1) and adjuvant AS02A	·         Strong Th-2 biased response
	4.       FMP2.1/AS01B ·         FMP2.1, in which E. coli expressed Apical membrane antigen (AMA-1) and adjuvant AS01B	·         Adverse effect (rashes after 18 days of vaccination)
	5.       AMA-C1/Alhydrogel + CPG 7909 ·         Pichia pastoris expressed Apical membrane antigen (AMA-1) with both FVO and 3D7 strains and adjuvants Alhydrogel + CPG 7909	·         Reduction of hemoglobin ·
	6.       AdCh63 AMA-1/MVA AMA-1 ·         Apical membrane antigen-1 (AMA-1) expressed and boosted with AdCh63 and MVA vectors	·         CD4+ responses are higher than CD8+ response
	7.       EBA175RII ·         Erythrocyte binding antigen (EBA) in merozoites and highly conserved region of Pf	·         Safe and immunogenic
	8.       SERA5 ·         Blood stage antigen in trophozoites and schizonts (SE36 expressed in E. coli acts as fragment of SERA5 antigen)	·         Safe and 100% seroconversion
	9.       BSAM-2/Alhydrogel +CPG ·         combination vaccine including MSP1 and AMA1 components. It contains a mixture of recombinant proteins with equal parts P. pastoris expressing FVO and 3D7 strains of AMA1 and E. coli expressing the FVO and 3D7 strains of MSP1.	·         Under evaluation
	10.   JAIVAC ·         This combination vaccine consists of MSP1 and EBA175, each of which is an E. coli expressed recombinant protein adjuvanted with Montanide ISA 720	·         Synergistic effects
	11.   GMZ2 ·         L. lactis expressed recombinant fusion protein of glutamate rich protein (GLURP) and MSP-3 adjuvanted with Al(OH)3	·         Acceptable safety ·         Both IgG and memory B cell response
	12.   Combination B (RESA, MSP-1, MSP-2) 13.   FMP1/AS02A 14.   MSP-1-C1/AlOH/AlOH + CPG 15.   MSP2-C1/ISA720 16.   AMA1-C1/ISA720 17.   AMA-FVO 18.   PfCP2.9	·         Already terminated (No succeed)
Gametocyte (Transmission Blocking) Vaccines	1.       Pfs25 ·         Ookinete surface protein Pfs25 ·         The antigen preparations including ookinete surface protein Pfs25, and the gametocyte antigens Pfs48/45 and Pfs230 are used in the TBV vaccines. Pfs25 was the first antigen to progress clinically but the reactogenicity was found to be very low.	·         Low reactogenicity
	2.       Pfs48/45 and Pfs230 ·         Contain the gametocyte antigens Pfs48/45 and Pfs230	·         Low reactogenicity
Combined Vaccines	1.       NMRC-M3V-D/Ad-PfCA Prime/Boost and NMRC-M3V-Ad-PfCA ·         DNA based vaccine containing CS antigen with AMA-1 antigen boosted with Adenovirus-5-vectors	·         Increase CD8+ T cell response but no sterile protection
	2.       CS AMA1 Virosomes ·         Synthetic peptide vaccines ·         Phosphatidylethanolamine (PE) conjugates on the surface of immunopotentiating reconstituted influenza virosomes (PEV301 and PEV302)	·         No sterile protection
	3.       SPf66 ·         Synthetic polypeptide vaccine consisting of CS and merozoites protein1 (MSP1) epitopes adjuvanted with alum	·         Low vaccine efficacy
	4.       RTS,S/AS02 (CS) and FMP-1/AS02 (MSP1) ·         Mixing RTS,S/AS02 (CS) and FMP-1/AS02 (MSP1) with both CS and MSP1 antigens	·         FMP1 gave no protection in the challenge model
P. vivax Vaccines	1.       PvCSP ·         Circumsporozoite protein from P. vivax	·         Under clinical trails
	2.       ChAd63-MVA PvDBP RII and PvDBP RII/GLA-SE ·         Extracellular, cysteine-rich region II (P. vivax Duffy-binding protein; PvDBP_RII)	·         Under clinical trails

Detection of OXA-48 Gene in Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae from Urine Samples

Infection and Drug Resistance 2020:13 2311–2321

Detection of OXA-48 Gene in Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae from Urine Samples

Sushma Gurung¹ Sonali Kafle² Binod Dhungel¹ Nabaraj Adhikari¹ Upendra Thapa Shrestha¹

Bipin Adhikari³ Megha Raj Banjara¹ Komal Raj Rijal¹ Prakash Ghimire¹

 

¹Central Department of Microbiology, Tribhuvan University, Kirtipur, Kathmandu, Nepal; 

²Alka Hospital, Lalitpur, Nepal;

³Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK

 

ABSTRACT

Introduction: Resistance to carbapenem in Gram-negative bacteria is attributable to their ability to produce carbapenemase enzymes. The main objective of this study was to detect the presence of blaOXA-48 genes in carbapenem-resistant uropathogenic Escherichia coli and Klebsiella pneumoniae isolated from urine samples from patients attending Alka Hospital, Jawalakhel, Lalitpur, Nepal.

 

Methods: A total of 1013 mid-stream urine samples were collected from patients with suspected urinary tract infection (UTI) between April and September 2018. The identified isolates underwent antibiotic susceptibility testing using the modified Kirby–Bauer disc diffusion method. Phenotypic carbapenemase production was confirmed by the modified Hodge test, and the blaOXA-48 gene was detected using conventional polymerase chain reaction.

 

Results: Out of 1013 urine samples, 15.2% (154/1013) had bacterial growth. Among the isolates, 91.5% (141/154) were Gram-negative bacteria, and E. coli was the most common bacterial isolate (62.9%; 97/154), followed by K. pneumoniae 15.6% (24/154). Among 121 bacterial isolates (97 E. coli isolates and 24 K. pneumoniae isolates), 70.3% (52/121) were multidrug-resistant E. coli and 29.7% (22/121) were multidrug-resistant K. pneumoniae. In addition, 9.1% (11/121) were carbapenem resistant (both imipenem and meropenem resistant). Development of multidrug resistance and development of carbapenem resistance were significantly associated (p<0.05). Of the 11 carbapenem-resistant isolates, only seven were carbapenemase producers; of these, 28.6% (2/7) were E. coli, 72.4% (5/7) were K. pneumoniae and 42.8% (3/7) had the blaOXA-48 gene. Of the three bacterial isolates with the blaOXA-48 gene, 33.3% (1/3) were E. coli and 66.7% (2/3) were K. pneumoniae.

 

Conclusion: One in ten isolates of E. coli and K. pneumoniae were carbapenem resistant. Among carbapenem-resistant isolates, one-third of E. coli and two-thirds of K. pneumoniae had the blaOXA-48 gene. OXA-48 serves as a potential agent to map the distribution of resistance among clinical isolates.

 

Keywords: antimicrobial resistance, AMR, carbapenem, carbapenemase, modified Hodge test, MHT, blaOXA-48 gene

 

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Article on Infection and Drug Resistance

Plasmid Profiling and Occurrence of β-Lactamase Enzymes in Multidrug-Resistant Uropathogenic Escherichia coli in Kathmandu, Nepal

Upendra Thapa Shrestha ^# 1 2, Sabnum Shrestha ^# 1, Nabaraj Adhikari ^1 2, Komal Raj Rijal ², Basudha Shrestha ³, Bipin Adhikari ⁴, Megha Raj Banjara ², Prakash Ghimire ²

Affiliations expand

·         PMID: 32606839

PMCID: PMC7320882

 

·         DOI: 10.2147/IDR.S250591

Free PMC article

Abstract

Introduction: Extended-spectrum β-lactamases (ESBL) among Gram-negative bacteria, predominantly Escherichia coli (E. coli), in Nepal, have been rising. The main objectives of this study were to determine the prevalence of uropathogenic E. coli, antibiotic resistance, ESBLs, ABLs (AmpC type β-lactamases), MBLs (metallo-β-lactamases) and KPCs (Klebsiella pneumoniae carbapenemases) and their correlation with plasmid profiling patterns among patients with urinary tract infections in a tertiary hospital in Kathmandu, Nepal.

Methods: The mid-stream urine samples collected from patients were inoculated in cystine-lactose-electrolyte-deficient (CLED) agar plates. E. coli producing ESBLs, ABLs, MBLs/KPC were identified phenotypically using standard microbiological methods. Plasmids were extracted by alkaline lysis method from E. coli isolates and profiled using agarose gel electrophoresis.

Results: Out of the total 2661 urine samples, E. coli were isolated in 64.34% (507/788), among which 170 (33.53%) were multidrug-resistant (MDR) isolates. All MDR isolates were resistant to amoxicillin and third-generation cephalosporins but were highly sensitive to imipenem (94.12%, 160/170), amikacin (92.94%, 158/170) and nitrofurantoin (86.47%, 147/170). Among 170 MDR isolates, 78.2% (133/170) were ESBLs, 46.3% (50/170) were AmpC, 11.2% (19/170) were MBL and 0.6% (1/170) were KPC producers. Coproduction of β-lactamases was detected in 24.12% (41/170) of isolates. E. coli isolates showed one plasmid (>33.5 kb), which was present in all the isolates. Overall, 44 different plasmid profile groups were identified based on molecular weight and number of plasmids. β-Lactamase producers were relatively resistant to the higher number of antibiotics tested (≤10) than non-producers (≤8), and the number of plasmids were higher in β-lactamase producers (≤7) than those in non-producers (≤5).

Conclusion: The higher prevalence of the ESBLs, AmpCs, KPCs and MBLs along with their coproduction in E. coli isolates highlights the importance of routine surveillance of ESBLs, AmpCs, KPCs and MBLs in microbiology laboratories using various phenotypic methods.

Keywords: AmpC type β-lactamases; ESBL; KPC; Klebsiella pneumoniae carbapenemases; MBL; antibiotic resistance; extended-spectrum β-lactamases; metallo-β-lactamases; uropathogenic Escherichia coli.

. 2020 Jun 23;13:1905-1917. 

doi: 10.2147/IDR.S250591. eCollection 2020.

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