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'''RTS,S/AS01''' (trade name '''Mosquirix''') is a recombinant protein-based [[malaria vaccine]].
'''RTS,S/AS01''' (trade name '''Mosquirix''') is a recombinant protein-based [[malaria vaccine]].


Approved for use by European regulators in July 2015,<ref>{{cite web | title=Mosquirix H-W-2300 | publisher=[[European Medicines Agency]] (EMA) | url=https://www.ema.europa.eu/en/mosquirix-h-w-2300 | access-date=4 March 2021}}</ref> it is the world's first licensed malaria vaccine and also the first vaccine licensed for use against a human [[parasitic disease]] of any kind.<ref name=BBC2015/> The RTS,S vaccine was conceived of and created in the late 1980s by scientists working at SmithKline Beecham Biologicals (now [[GlaxoSmithKline]] Vaccines) laboratories in Belgium.<ref>{{Cite web|url=http://www.google.com/patents/EP0614465B1?cl=3Den|title = HYBRID PROTEIN BETWEEN CS FROM PLASMODIUM AND HBsAG}}</ref> The vaccine was further developed through a collaboration between GSK and the [[Walter Reed Army Institute of Research]]<ref>{{cite journal |vauthors=Heppner DG, Kester KE, Ockenhouse CF, et al. |title=Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research |journal=Vaccine |volume=23 |issue=17–18 |pages=2243–50 |year=2005 |pmid=15755604 |doi=10.1016/j.vaccine.2005.01.142|url=http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1019&context=usarmyresearch }}</ref> and has been funded in part by the [[PATH (global health organization)|PATH Malaria Vaccine Initiative]] and the [[Bill and Melinda Gates Foundation]]. Its [[vaccine efficacy|efficacy]] ranges from 26 to 50% in infants and young children. On 23 October 2015, the [[World Health Organization]]'s [[Strategic Advisory Group of Experts|Strategic Advisory Group of Experts on Immunization]] (SAGE) and the [[Malaria Policy Advisory Committee]] (MPAC) jointly recommended a pilot implementation of the vaccine in Africa.<ref>{{Cite web|url=http://who.int/mediacentre/news/releases/2015/sage/en/|title=Pilot implementation of first malaria vaccine recommended by WHO advisory groups}}</ref>
Approved for use by European regulators in July 2015,<ref>{{cite web | title=Mosquirix H-W-2300 | publisher=[[European Medicines Agency]] (EMA) | url=https://www.ema.europa.eu/en/mosquirix-h-w-2300 | access-date=4 March 2021}}</ref> it is the world's first licensed malaria vaccine and also the first vaccine licensed for use against a human [[parasitic disease]] of any kind.<ref name=BBC2015/> The RTS,S vaccine was conceived of and created in the late 1980s by scientists working at SmithKline Beecham Biologicals (now [[GlaxoSmithKline]] Vaccines) laboratories in Belgium.<ref>{{Cite web|url=http://www.google.com/patents/EP0614465B1?cl=3Den|title = HYBRID PROTEIN BETWEEN CS FROM PLASMODIUM AND HBsAG}}</ref> The vaccine was further developed through a collaboration between GSK and the [[Walter Reed Army Institute of Research]]<ref name=":0">{{cite journal |vauthors=Heppner DG, Kester KE, Ockenhouse CF, et al. |title=Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research |journal=Vaccine |volume=23 |issue=17–18 |pages=2243–50 |year=2005 |pmid=15755604 |doi=10.1016/j.vaccine.2005.01.142|url=http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1019&context=usarmyresearch }}</ref> and has been funded in part by the [[PATH (global health organization)|PATH Malaria Vaccine Initiative]] and the [[Bill and Melinda Gates Foundation]]. Its [[vaccine efficacy|efficacy]] ranges from 26 to 50% in infants and young children. On 23 October 2015, the [[World Health Organization]]'s [[Strategic Advisory Group of Experts|Strategic Advisory Group of Experts on Immunization]] (SAGE) and the [[Malaria Policy Advisory Committee]] (MPAC) jointly recommended a pilot implementation of the vaccine in Africa.<ref>{{Cite web|url=http://who.int/mediacentre/news/releases/2015/sage/en/|title=Pilot implementation of first malaria vaccine recommended by WHO advisory groups}}</ref>


This pilot project for vaccination was launched on 23 April 2019 in [[Malawi]], on 30 April 2019 in [[Ghana]], and on 13 September 2019 in [[Kenya]].<ref name="Wuxi">{{cite press release |last=Alonso |first=Pedro |date=19 June 2019 |title=Letter to partners – June 2019 |url=https://www.who.int/news-room/detail/19-06-2019-letter-to-partners-june-2019 |location=Wuxi |publisher=World Health Organization |access-date=2019-10-22}}</ref><ref name="Homa">{{cite press release |author=<!--Staff writer(s); no by-line.--> |title=Malaria vaccine launched in Kenya: Kenya joins Ghana and Malawi to roll out landmark vaccine in pilot introduction |url=https://www.afro.who.int/news/malaria-vaccine-launched-kenya-kenya-joins-ghana-and-malawi-roll-out-landmark-vaccine-pilot |location=Homa Bay |publisher=World Health Organization |date=13 September 2019 |access-date=2019-10-22}}</ref> In October 2021 the vaccine was endorsed by the World Health Organization for "broad use" in children, the first malaria vaccine candidate ever to reach this recommendation.<ref>{{cite news |last1=Davies |first1=Lizzy |title=WHO endorses use of world’s first malaria vaccine in Africa |url=https://www.theguardian.com/global-development/2021/oct/06/who-endorses-use-of-worlds-first-malaria-vaccine-in-africa |access-date=6 October 2021 |work=The Guardian |date=6 October 2021 |language=en}}</ref><ref>{{cite web |last1=Drysdale |first1=Carla |last2=Kelleher |first2=Kristen |title=WHO recommends groundbreaking malaria vaccine for children at risk |url=https://www.who.int/news/item/06-10-2021-who-recommends-groundbreaking-malaria-vaccine-for-children-at-risk |publisher=[[World Health Organization]] |access-date=6 October 2021}}</ref>
This pilot project for vaccination was launched on 23 April 2019 in [[Malawi]], on 30 April 2019 in [[Ghana]], and on 13 September 2019 in [[Kenya]].<ref name="Wuxi">{{cite press release |last=Alonso |first=Pedro |date=19 June 2019 |title=Letter to partners – June 2019 |url=https://www.who.int/news-room/detail/19-06-2019-letter-to-partners-june-2019 |location=Wuxi |publisher=World Health Organization |access-date=2019-10-22}}</ref><ref name="Homa">{{cite press release |author=<!--Staff writer(s); no by-line.--> |title=Malaria vaccine launched in Kenya: Kenya joins Ghana and Malawi to roll out landmark vaccine in pilot introduction |url=https://www.afro.who.int/news/malaria-vaccine-launched-kenya-kenya-joins-ghana-and-malawi-roll-out-landmark-vaccine-pilot |location=Homa Bay |publisher=World Health Organization |date=13 September 2019 |access-date=2019-10-22}}</ref> In October 2021 the vaccine was endorsed by the World Health Organization for "broad use" in children, the first malaria vaccine candidate ever to reach this recommendation.<ref>{{cite news |last1=Davies |first1=Lizzy |title=WHO endorses use of world’s first malaria vaccine in Africa |url=https://www.theguardian.com/global-development/2021/oct/06/who-endorses-use-of-worlds-first-malaria-vaccine-in-africa |access-date=6 October 2021 |work=The Guardian |date=6 October 2021 |language=en}}</ref><ref>{{cite web |last1=Drysdale |first1=Carla |last2=Kelleher |first2=Kristen |title=WHO recommends groundbreaking malaria vaccine for children at risk |url=https://www.who.int/news/item/06-10-2021-who-recommends-groundbreaking-malaria-vaccine-for-children-at-risk |publisher=[[World Health Organization]] |access-date=6 October 2021}}</ref>
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== Components and mechanism ==
== Components and mechanism ==
The RTS,S vaccine was engineered using genes from the repeat and T-cell epitope in the pre-erythrocytic [[circumsporozoite protein]] (CSP) of the ''[[Plasmodium falciparum]]'' malaria parasite and a viral envelope protein of the hepatitis B virus ([[HBsAg]]), to which was added a chemical [[adjuvant]] (AS01) to increase the immune system response.<ref>{{cite journal |title=Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial |journal=Lancet |volume=386 |issue=9988 |pages=31–45 |year=2015 |pmid=25913272 |pmc=5626001 |doi=10.1016/S0140-6736(15)60721-8|author=RTS,S Clinical Trials Partnership}}</ref> Infection is prevented by inducing [[humoral immunity|humoral]] and [[cellular immunity]], with high antibody titers, that block the parasite from infecting the liver.<ref>{{cite journal |doi=10.1172/JCI70349 |title=Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent Plasmodium falciparum infection |year=2014 |journal=Journal of Clinical Investigation |volume=124 |issue=1 |pages=140–4 |pmid=24292709 |last1=Foquet |first1=Lander |last2=Hermsen |first2=Cornelus |last3=van Gemert |first3=Geert-Jan |last4=Van Braeckel |first4=Eva |last5=Weening |first5=Karin |last6=Sauerwein |first6=Robert |last7=Meuleman |first7=Philip |last8=Leroux-Roels |first8=Geert |pmc=3871238}}</ref>
The RTS,S vaccine is based on a protein construct first developed by [[GlaxoSmithKline]] in 1986, and named RTS because it was engineered using genes from the repeat ('R') and T-cell epitope ('T') of the pre-erythrocytic [[circumsporozoite protein]] (CSP) of the ''[[Plasmodium falciparum]]'' malaria parasite together with a viral surface antigen ('S') of the hepatitis B virus ([[HBsAg]]) <ref name=":0" />. To improve purification properties, additional surface antigen was added and the resulting construct was called RTS,S.<ref name=":0" />. A chemical [[adjuvant]] (AS01) was added to increase the immune system response.<ref>{{cite journal |title=Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial |journal=Lancet |volume=386 |issue=9988 |pages=31–45 |year=2015 |pmid=25913272 |pmc=5626001 |doi=10.1016/S0140-6736(15)60721-8|author=RTS,S Clinical Trials Partnership}}</ref> Infection is prevented by inducing [[humoral immunity|humoral]] and [[cellular immunity]], with high antibody titers, that block the parasite from infecting the liver.<ref>{{cite journal |doi=10.1172/JCI70349 |title=Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent Plasmodium falciparum infection |year=2014 |journal=Journal of Clinical Investigation |volume=124 |issue=1 |pages=140–4 |pmid=24292709 |last1=Foquet |first1=Lander |last2=Hermsen |first2=Cornelus |last3=van Gemert |first3=Geert-Jan |last4=Van Braeckel |first4=Eva |last5=Weening |first5=Karin |last6=Sauerwein |first6=Robert |last7=Meuleman |first7=Philip |last8=Leroux-Roels |first8=Geert |pmc=3871238}}</ref>


The T-cell epitope of CSP is O-fucosylated in ''[[Plasmodium falciparum]]''<ref>{{cite journal|last1=Swearingen|first1=Kristian E.|last2=Lindner|first2=Scott E.|last3=Shi|first3=Lirong|last4=Shears|first4=Melanie J.|last5=Harupa|first5=Anke|last6=Hopp|first6=Christine S.|last7=Vaughan|first7=Ashley M.|last8=Springer|first8=Timothy A.|last9=Moritz|first9=Robert L.|last10=Kappe|first10=Stefan H. I.|last11=Sinnis|first11=Photini|title=Interrogating the Plasmodium Sporozoite Surface: Identification of Surface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP by Mass Spectrometry-Based Proteomics|journal=PLOS Pathogens|date=29 April 2016|volume=12|issue=4|pages=e1005606|doi=10.1371/journal.ppat.1005606|pmid=27128092|pmc=4851412|issn=1553-7374}}</ref><ref>{{cite journal|last1=Lopaticki|first1=Sash|title=Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts|journal=Nature Communications|volume=8|last2=Yang|first2=Annie S. P.|last3=John|first3=Alan|last4=Scott|first4=Nichollas E.|last5=Lingford|first5=James P.|last6=O’Neill|first6=Matthew T.|last7=Erickson|first7=Sara M.|last8=McKenzie|first8=Nicole C.|last9=Jennison|first9=Charlie|last10=Whitehead|first10=Lachlan W.|last11=Douglas|first11=Donna N.|last12=Kneteman|first12=Norman M.|last13=Goddard-Borger|first13=Ethan D.|last14=Boddey|first14=Justin A.|doi=10.1038/s41467-017-00571-y|pmid=28916755|language=En|issn=2041-1723|year=2017|issue=1|page=561|pmc=5601480|bibcode=2017NatCo...8..561L}}</ref> and ''[[Plasmodium vivax]]'',<ref>{{cite journal|last1=Swearingen|first1=Kristian E.|last2=Lindner|first2=Scott E.|last3=Flannery|first3=Erika L.|last4=Vaughan|first4=Ashley M.|last5=Morrison|first5=Robert D.|last6=Patrapuvich|first6=Rapatbhorn|last7=Koepfli|first7=Cristian|last8=Muller|first8=Ivo|last9=Jex|first9=Aaron|last10=Moritz|first10=Robert L.|last11=Kappe|first11=Stefan H. I.|last12=Sattabongkot|first12=Jetsumon|last13=Mikolajczak|first13=Sebastian A.|title=Proteogenomic analysis of the total and surface-exposed proteomes of Plasmodium vivax salivary gland sporozoites|journal=PLOS Neglected Tropical Diseases|date=31 July 2017|volume=11|issue=7|pages=e0005791|doi=10.1371/journal.pntd.0005791|pmid=28759593|issn=1935-2735|pmc=5552340}}</ref> while the RTS,S vaccine produced in yeast is not.
The T-cell epitope of CSP is O-fucosylated in ''[[Plasmodium falciparum]]''<ref>{{cite journal|last1=Swearingen|first1=Kristian E.|last2=Lindner|first2=Scott E.|last3=Shi|first3=Lirong|last4=Shears|first4=Melanie J.|last5=Harupa|first5=Anke|last6=Hopp|first6=Christine S.|last7=Vaughan|first7=Ashley M.|last8=Springer|first8=Timothy A.|last9=Moritz|first9=Robert L.|last10=Kappe|first10=Stefan H. I.|last11=Sinnis|first11=Photini|title=Interrogating the Plasmodium Sporozoite Surface: Identification of Surface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP by Mass Spectrometry-Based Proteomics|journal=PLOS Pathogens|date=29 April 2016|volume=12|issue=4|pages=e1005606|doi=10.1371/journal.ppat.1005606|pmid=27128092|pmc=4851412|issn=1553-7374}}</ref><ref>{{cite journal|last1=Lopaticki|first1=Sash|title=Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts|journal=Nature Communications|volume=8|last2=Yang|first2=Annie S. P.|last3=John|first3=Alan|last4=Scott|first4=Nichollas E.|last5=Lingford|first5=James P.|last6=O’Neill|first6=Matthew T.|last7=Erickson|first7=Sara M.|last8=McKenzie|first8=Nicole C.|last9=Jennison|first9=Charlie|last10=Whitehead|first10=Lachlan W.|last11=Douglas|first11=Donna N.|last12=Kneteman|first12=Norman M.|last13=Goddard-Borger|first13=Ethan D.|last14=Boddey|first14=Justin A.|doi=10.1038/s41467-017-00571-y|pmid=28916755|language=En|issn=2041-1723|year=2017|issue=1|page=561|pmc=5601480|bibcode=2017NatCo...8..561L}}</ref> and ''[[Plasmodium vivax]]'',<ref>{{cite journal|last1=Swearingen|first1=Kristian E.|last2=Lindner|first2=Scott E.|last3=Flannery|first3=Erika L.|last4=Vaughan|first4=Ashley M.|last5=Morrison|first5=Robert D.|last6=Patrapuvich|first6=Rapatbhorn|last7=Koepfli|first7=Cristian|last8=Muller|first8=Ivo|last9=Jex|first9=Aaron|last10=Moritz|first10=Robert L.|last11=Kappe|first11=Stefan H. I.|last12=Sattabongkot|first12=Jetsumon|last13=Mikolajczak|first13=Sebastian A.|title=Proteogenomic analysis of the total and surface-exposed proteomes of Plasmodium vivax salivary gland sporozoites|journal=PLOS Neglected Tropical Diseases|date=31 July 2017|volume=11|issue=7|pages=e0005791|doi=10.1371/journal.pntd.0005791|pmid=28759593|issn=1935-2735|pmc=5552340}}</ref> while the RTS,S vaccine produced in yeast is not.

Revision as of 17:04, 6 October 2021

RTS,S/AS01 (trade name Mosquirix) is a recombinant protein-based malaria vaccine.

Approved for use by European regulators in July 2015,[1] it is the world's first licensed malaria vaccine and also the first vaccine licensed for use against a human parasitic disease of any kind.[2] The RTS,S vaccine was conceived of and created in the late 1980s by scientists working at SmithKline Beecham Biologicals (now GlaxoSmithKline Vaccines) laboratories in Belgium.[3] The vaccine was further developed through a collaboration between GSK and the Walter Reed Army Institute of Research[4] and has been funded in part by the PATH Malaria Vaccine Initiative and the Bill and Melinda Gates Foundation. Its efficacy ranges from 26 to 50% in infants and young children. On 23 October 2015, the World Health Organization's Strategic Advisory Group of Experts on Immunization (SAGE) and the Malaria Policy Advisory Committee (MPAC) jointly recommended a pilot implementation of the vaccine in Africa.[5]

This pilot project for vaccination was launched on 23 April 2019 in Malawi, on 30 April 2019 in Ghana, and on 13 September 2019 in Kenya.[6][7] In October 2021 the vaccine was endorsed by the World Health Organization for "broad use" in children, the first malaria vaccine candidate ever to reach this recommendation.[8][9]

History

Potential malaria vaccines have been an intense area of research since the 1960s.[10] SPf66 was tested extensively in endemic areas in the 1990s, but clinical trials showed it to be insufficiently effective.[11] Other vaccine candidates, targeting the blood-stage of the malaria parasite's life cycle, have also been insufficient on their own.[12] Among several potential vaccines under development that target the pre-erythrocytic stage of the disease, RTS,S has shown the most promising results so far.[13]

RTS,S has been funded, most recently, by the non-profit PATH Malaria Vaccine Initiative (MVI) and GlaxoSmithKline with funding from the Bill and Melinda Gates Foundation.[14]

The RTS,S-based vaccine formulation had previously been demonstrated to be safe, well tolerated, immunogenic, and to potentially confer partial efficacy in both malaria-naive and -experienced adults as well as children.[15]

The EMA approved the RTS,S vaccine in July 2015, with a recommendation that it be used in Africa for babies at risk of getting malaria. RTS,S was the world's first malaria vaccine to get approval for this use.[16][2] After additional regulatory decisions by the World Health Organization, and individual African country governments, a "roll out" of the product could come as early as 2017.

Preliminary research suggests that delayed fractional dosing could increase the vaccine's efficacy up to 86%.[17][18]

On 17 November 2016, WHO announced that the RTS,S vaccine would be rolled out in pilot projects in 3 countries in sub-Saharan Africa. The pilot programme, coordinated by WHO, will assess the extent to which the vaccine's protective effect shown in advanced clinical trials can be replicated in real-life settings. Specifically, the programme will evaluate the feasibility of delivering the required 4 doses of the vaccine; the impact of the vaccine on lives saved; and the safety of the vaccine in the context of routine use.[19]

Vaccinations by the ministries of health of Malawi, Ghana, and Kenya began in April and September 2019 and target 360,000 children per year in areas where vaccination would have the highest impact. The results are planned to be used by the World Health Organization to advise about a possible future deployment of the vaccine.[6][7][20] In 2021 it was reported that the vaccine together with other anti-malaria medication when given at the most vulnerable season could reduce deaths and illness from the disease by 70%[21][22]

Components and mechanism

The RTS,S vaccine is based on a protein construct first developed by GlaxoSmithKline in 1986, and named RTS because it was engineered using genes from the repeat ('R') and T-cell epitope ('T') of the pre-erythrocytic circumsporozoite protein (CSP) of the Plasmodium falciparum malaria parasite together with a viral surface antigen ('S') of the hepatitis B virus (HBsAg) [4]. To improve purification properties, additional surface antigen was added and the resulting construct was called RTS,S.[4]. A chemical adjuvant (AS01) was added to increase the immune system response.[23] Infection is prevented by inducing humoral and cellular immunity, with high antibody titers, that block the parasite from infecting the liver.[24]

The T-cell epitope of CSP is O-fucosylated in Plasmodium falciparum[25][26] and Plasmodium vivax,[27] while the RTS,S vaccine produced in yeast is not.

See also

References

  1. ^ "Mosquirix H-W-2300". European Medicines Agency (EMA). Retrieved 4 March 2021.
  2. ^ a b Walsh, Fergus (24 July 2015). "Malaria vaccine gets 'green light'". BBC. Retrieved 25 July 2015.
  3. ^ "HYBRID PROTEIN BETWEEN CS FROM PLASMODIUM AND HBsAG".
  4. ^ a b c Heppner DG, Kester KE, Ockenhouse CF, et al. (2005). "Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research". Vaccine. 23 (17–18): 2243–50. doi:10.1016/j.vaccine.2005.01.142. PMID 15755604.
  5. ^ "Pilot implementation of first malaria vaccine recommended by WHO advisory groups".
  6. ^ a b Alonso, Pedro (19 June 2019). "Letter to partners – June 2019" (Press release). Wuxi: World Health Organization. Retrieved 2019-10-22.
  7. ^ a b "Malaria vaccine launched in Kenya: Kenya joins Ghana and Malawi to roll out landmark vaccine in pilot introduction" (Press release). Homa Bay: World Health Organization. 13 September 2019. Retrieved 2019-10-22.
  8. ^ Davies, Lizzy (6 October 2021). "WHO endorses use of world's first malaria vaccine in Africa". The Guardian. Retrieved 6 October 2021.
  9. ^ Drysdale, Carla; Kelleher, Kristen. "WHO recommends groundbreaking malaria vaccine for children at risk". World Health Organization. Retrieved 6 October 2021.
  10. ^ Hill AV (2011). "Vaccines against malaria". Philos. Trans. R. Soc. Lond. B Biol. Sci. 366 (1579): 2806–14. doi:10.1098/rstb.2011.0091. PMC 3146776. PMID 21893544.
  11. ^ Graves, Patricia M; Gelband, Hellen (2006). Graves, Patricia M (ed.). "Vaccines for preventing malaria (SPf66)". Cochrane Database of Systematic Reviews (2): CD005966. doi:10.1002/14651858.CD005966. PMC 6532709. PMID 16625647.
  12. ^ Graves, Patricia M; Gelband, Hellen (2006). Graves, Patricia M (ed.). "Vaccines for preventing malaria (blood-stage)". Cochrane Database of Systematic Reviews (4): CD006199. doi:10.1002/14651858.CD006199. PMC 6532641. PMID 17054281.
  13. ^ Graves, Patricia M; Gelband, Hellen (2006). Graves, Patricia M (ed.). "Vaccines for preventing malaria (pre-erythrocytic)". Cochrane Database of Systematic Reviews (4): CD006198. doi:10.1002/14651858.CD006198. PMC 6532586. PMID 17054280.
  14. ^ Stein, Rob (October 18, 2011). "Experimental malaria vaccine protects many children, study shows". Washington Post.
  15. ^ Regules, Jason A; Cummings, James F; Ockenhouse, Christian F (2011). "The RTS,S vaccine candidate for malaria". Expert Review of Vaccines. 10 (5): 589–99. doi:10.1586/erv.11.57. PMID 21604980. S2CID 20443829.
  16. ^ "First malaria vaccine receives positive scientific opinion from EMA". European Medicines Agency. 24 July 2015. Retrieved 24 July 2015.
  17. ^ Birkett, Ashley (September 16, 2016). "A vaccine for malaria elimination?". PATH.
  18. ^ Regules JA, Cicatelli SB, Bennett JW, et al. (2016). "Fractional Third and Fourth Dose of RTS,S/AS01 Malaria Candidate Vaccine: A Phase 2a Controlled Human Malaria Parasite Infection and Immunogenicity Study". J. Infect. Dis. 214 (5): 762–71. doi:10.1093/infdis/jiw237. PMID 27296848.
  19. ^ "Malaria: The malaria vaccine implementation programme (MVIP)".
  20. ^ "WHO | MVIP countries: Ghana, Kenya and Malawi".
  21. ^ Chandramohan, Daniel; Zongo, Issaka; Sagara, Issaka; Cairns, Matthew; Yerbanga, Rakiswendé-Serge; Diarra, Modibo; Nikièma, Frédéric; Tapily, Amadou; Sompougdou, Frédéric; Issiaka, Djibrilla; Zoungrana, Charles (2021-08-25). "Seasonal Malaria Vaccination with or without Seasonal Malaria Chemoprevention". New England Journal of Medicine. 0 (0): null. doi:10.1056/NEJMoa2026330. ISSN 0028-4793.
  22. ^ "Trial suggests malaria sickness could be cut by 70%". BBC News. 2021-08-26. Retrieved 2021-08-26.
  23. ^ RTS,S Clinical Trials Partnership (2015). "Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial". Lancet. 386 (9988): 31–45. doi:10.1016/S0140-6736(15)60721-8. PMC 5626001. PMID 25913272.
  24. ^ Foquet, Lander; Hermsen, Cornelus; van Gemert, Geert-Jan; Van Braeckel, Eva; Weening, Karin; Sauerwein, Robert; Meuleman, Philip; Leroux-Roels, Geert (2014). "Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent Plasmodium falciparum infection". Journal of Clinical Investigation. 124 (1): 140–4. doi:10.1172/JCI70349. PMC 3871238. PMID 24292709.
  25. ^ Swearingen, Kristian E.; Lindner, Scott E.; Shi, Lirong; Shears, Melanie J.; Harupa, Anke; Hopp, Christine S.; Vaughan, Ashley M.; Springer, Timothy A.; Moritz, Robert L.; Kappe, Stefan H. I.; Sinnis, Photini (29 April 2016). "Interrogating the Plasmodium Sporozoite Surface: Identification of Surface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP by Mass Spectrometry-Based Proteomics". PLOS Pathogens. 12 (4): e1005606. doi:10.1371/journal.ppat.1005606. ISSN 1553-7374. PMC 4851412. PMID 27128092.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  26. ^ Lopaticki, Sash; Yang, Annie S. P.; John, Alan; Scott, Nichollas E.; Lingford, James P.; O’Neill, Matthew T.; Erickson, Sara M.; McKenzie, Nicole C.; Jennison, Charlie; Whitehead, Lachlan W.; Douglas, Donna N.; Kneteman, Norman M.; Goddard-Borger, Ethan D.; Boddey, Justin A. (2017). "Protein O-fucosylation in Plasmodium falciparum ensures efficient infection of mosquito and vertebrate hosts". Nature Communications. 8 (1): 561. Bibcode:2017NatCo...8..561L. doi:10.1038/s41467-017-00571-y. ISSN 2041-1723. PMC 5601480. PMID 28916755.
  27. ^ Swearingen, Kristian E.; Lindner, Scott E.; Flannery, Erika L.; Vaughan, Ashley M.; Morrison, Robert D.; Patrapuvich, Rapatbhorn; Koepfli, Cristian; Muller, Ivo; Jex, Aaron; Moritz, Robert L.; Kappe, Stefan H. I.; Sattabongkot, Jetsumon; Mikolajczak, Sebastian A. (31 July 2017). "Proteogenomic analysis of the total and surface-exposed proteomes of Plasmodium vivax salivary gland sporozoites". PLOS Neglected Tropical Diseases. 11 (7): e0005791. doi:10.1371/journal.pntd.0005791. ISSN 1935-2735. PMC 5552340. PMID 28759593.{{cite journal}}: CS1 maint: unflagged free DOI (link)

Further reading

  • Wilby, K. J.; Lau, T. T.; Gilchrist, S. E.; Ensom, M. H. (2012). "Mosquirix (RTS,S): A Novel Vaccine for the Prevention of Plasmodium falciparum Malaria". Annals of Pharmacotherapy. 46 (3): 384–93. doi:10.1345/aph.1Q634. PMID 22408046.
  • Asante, Kwaku Poku; et al. (2011). "Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial". The Lancet Infectious Diseases. 11 (10): 741–9. doi:10.1016/S1473-3099(11)70100-1. PMID 21782519.
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