Efficacy model for mosquito stage transmission blocking vaccines for malaria

Parasitology ◽  
2008 ◽  
Vol 135 (13) ◽  
pp. 1497-1506 ◽  
Author(s):  
A. SAUL
Keyword(s):  
Herd Immunity ◽  
Field Trials ◽  
Host Population ◽  
Antibody Responses ◽  
Human Populations ◽  
Transmission Blocking ◽  
Antibody Levels ◽  
The Relationship ◽  
Transmission Blocking Vaccines ◽  
Field Setting

SUMMARYVaccines that target antigens found on the mosquito stages of Plasmodium falciparum and Plasmodium vivax parasites are under development as transmission blocking vaccines. Antisera from vaccinated animals and humans are able to block oocyst development in artificially fed mosquitoes but it is not clear from these data what level of antibody response would be required for a useful vaccine in a field setting. This paper describes a mathematical model that takes into account the relationship between antibody levels and blocking of oocyst levels in artificial feeds, the distribution of antibody responses seen in human populations and the distribution of oocyst densities in infected mosquitoes in the field to calculate the levels of antibody in the host population that would be required to achieve a level of herd immunity in a vaccinated human population that would give an operationally useful level of transmission blocking. The model predicts that current formulations of Pfs25 are likely to achieve useful reductions in transmission when tested in human field trials.

scholarly journals Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Puthupparampil V. Scaria ◽  
Charles Anderson ◽  
Olga Muratova ◽  
Nada Alani ◽  
Hung V. Trinh ◽  
...  
Keyword(s):  
Immune Responses ◽  
Malaria Transmission ◽  
Functional Activity ◽  
Rhesus Macaques ◽  
Transmission Blocking ◽  
Tlr4 Agonist ◽  
Functional Immunity ◽  
Antibody Levels ◽  
Transmission Blocking Vaccines ◽  
Better Than

AbstractMalaria transmission-blocking vaccines candidates based on Pfs25 and Pfs230 have advanced to clinical studies. Exoprotein A (EPA) conjugate of Pfs25 in Alhydrogel® developed functional immunity in humans, with limited durability. Pfs230 conjugated to EPA (Pfs230D1-EPA) with liposomal adjuvant AS01 is currently in clinical trials in Mali. Studies with these conjugates revealed that non-human primates are better than mice to recapitulate the human immunogenicity and functional activity. Here, we evaluated the effect of ALFQ, a liposomal adjuvant consisting of TLR4 agonist and QS21, on the immunogenicity of Pfs25-EPA and Pfs230D1-EPA in Rhesus macaques. Both conjugates generated strong antibody responses and functional activity after two vaccinations though activity declined rapidly. A third vaccination of Pfs230D1-EPA induced functional activity lasting at least 9 months. Antibody avidity increased with each vaccination and correlated strongly with functional activity. IgG subclass analysis showed induction of Th1 and Th2 subclass antibody levels that correlated with activity.

scholarly journals Titers, Prevalence, and Duration of SARS-CoV-2 Antibodies in a Local COVID-19 Outbreak and Following Vaccination

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 587
Author(s):  
Jodi F. Hedges ◽  
Macy A. Thompson ◽  
Deann T. Snyder ◽  
Amanda Robison ◽  
Matthew P. Taylor ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Herd Immunity ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Specific Antibodies ◽  
Neutralization Capacity ◽  
Protein Receptor ◽  
Asymptomatic Infections ◽  
Antibody Levels

Information concerning the development of neutralizing antibodies and their duration will be critical to establishing herd immunity for COVID-19. We sought to evaluate SARS-CoV-2 spike protein receptor-binding domain (RBD)-specific antibodies, their duration, and capacity for SARS-CoV-2 neutralization in volunteers while the pandemic spread within our community starting in March 2020. Those participants with the highest starting titers had the longest-lasting response, up to 12 months post-diagnosis. SARS-CoV-2 neutralization capacity was correlated with anti-RBD antibody levels. The majority of our participants with confirmed COVID-19 diagnosis had very mild or asymptomatic infections. We also detected low and largely non-neutralizing anti-RBD IgG titers in a few participants with no known COVID-19 diagnosis. Finally, we found that antibody responses induced by vaccination were significantly higher than those induced by natural infection. Thus, our study suggests that vaccination is still critical even for those naturally infected or diagnosed with COVID-19.

scholarly journals Antibodies to Malaria Vaccine Candidates Pvs25 and Pvs28 Completely Block the Ability of Plasmodium vivax To Infect Mosquitoes

2000 ◽  
Vol 68 (12) ◽  
pp. 6618-6623 ◽  
Author(s):  
Hajime Hisaeda ◽  
Anthony W. Stowers ◽  
Takafumi Tsuboi ◽  
William E. Collins ◽  
Jetsumon S. Sattabongkot ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Malaria Vaccine ◽  
Antibody Responses ◽  
Sexual Stage ◽  
Infected Blood ◽  
Transmission Blocking ◽  
Vaccine Candidates ◽  
Human Antibodies ◽  
Transmission Blocking Vaccines ◽  
Transmission Blocking Vaccine

ABSTRACT Transmission-blocking vaccines are one strategy for controlling malaria, whereby sexual-stage parasites are inhibited from infecting mosquitoes by human antibodies. To evaluate whether the recently clonedPlasmodium vivax proteins Pvs25 and Pvs28 are candidates for a transmission-blocking vaccine, the molecules were expressed in yeast as secreted recombinant proteins. Mice vaccinated with these proteins adsorbed to aluminum hydroxide developed strong antibody responses against the immunogens, although for Pvs28, this response was genetically restricted. Antisera against both recombinant Pvs25 and Pvs28 recognized the corresponding molecules expressed by cultured sexual-stage parasites isolated from patients with P. vivaxmalaria. The development of malaria parasites in mosquitoes was completely inhibited when these antisera were ingested with the infected blood meal. Pvs25 and Pvs28, expressed inSaccharomyces cerevisiae, are as yet the only fully characterized transmission-blocking vaccine candidates against P. vivax that induce such a potent antiparasite response.

scholarly journals Profiling the Quality and Quantity of Naturally Induced Antibody Responses Against Pfs230 and Pfs48/45 Among Non-Febrile Children Living in Southern Ghana: A Longitudinal Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Fermin K. Broni ◽  
Festus K. Acquah ◽  
Dorcas Obiri-Yeboah ◽  
Evans K. Obboh ◽  
Esther Sarpong ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Venous Blood ◽  
Dry Season ◽  
Antibody Responses ◽  
Clear Understanding ◽  
Older Children ◽  
Igg Antibody ◽  
Transmission Blocking ◽  
Antibody Levels ◽  
Transmission Blocking Vaccine

A clear understanding of the properties of naturally induced antibody responses against transmission-blocking vaccine candidates can accelerate the understanding of the development of transmission-blocking immunity. This study characterized the naturally induced IgG responses against two leading transmission-blocking vaccine antigens, Pfs230 and Pfs48/45, in non-febrile children living in Simiw, Ghana. Consecutive sampling was used to recruit 84 non-febrile children aged from 6 to 12 years old into the 6-month (November 2017 until May 2018) longitudinal study. Venous blood (1 ml) was collected once every 2 months and used to determine hemoglobin levels, P. falciparum prevalence using microscopy and polymerase chain reaction, and the levels and relative avidity of IgG responses against Pfs230 and Pfs48/45 using indirect ELISA. IgG levels against Pfs230 and Pfs48/45 decreased from the start (November) to the middle (January) and end (March) of the dry season respectively, then they began to increase. Participants, especially older children (10–12 years old) with active infections generally had lower antibody levels against both antigens. The relative avidities of IgG against both antigens followed the trend of IgG levels until the middle of the dry season, after which the relative avidities of both antigens correlated inversely with the antibody levels. In conclusion, although IgG antibody levels against both Pfs48/45 and Pfs230 began to increase by the early rainy season, they were inversely correlated to their respective relative avidities.

scholarly journals Characterization of Naturally Acquired Immunity to a Panel of Antigens Expressed in Mature P. falciparum Gametocytes

2021 ◽  
Vol 11 ◽  
Author(s):  
Michelle K. Muthui ◽  
Eizo Takashima ◽  
Brian R. Omondi ◽  
Christine Kinya ◽  
William I. Muasya ◽  
...  
Keyword(s):  
Antibody Responses ◽  
Acquired Immunity ◽  
Linear Regression Models ◽  
Transmission Blocking ◽  
Study Population ◽  
The Mean ◽  
Acquired Immune Responses ◽  
Antibody Levels ◽  
Variant Antigen

IntroductionNaturally acquired immune responses against antigens expressed on the surface of mature gametocytes develop in individuals living in malaria-endemic areas. Evidence suggests that such anti-gametocyte immunity can block the development of the parasite in the mosquito, thus playing a role in interrupting transmission. A better comprehension of naturally acquired immunity to these gametocyte antigens can aid the development of transmission-blocking vaccines and improve our understanding of the human infectious reservoir.MethodsAntigens expressed on the surface of mature gametocytes that had not previously been widely studied for evidence of naturally acquired immunity were identified for protein expression alongside Pfs230-C using either the mammalian HEK293E or the wheat germ cell-free expression systems. Where there was sequence variation in the candidate antigens (3D7 vs a clinical isolate PfKE04), both variants were expressed. ELISA was used to assess antibody responses against these antigens, as well as against crude stage V gametocyte extract (GE) and AMA1 using archived plasma samples from individuals recruited to participate in malaria cohort studies. We analyzed antibody levels (estimated from optical density units using a standardized ELISA) and seroprevalence (defined as antibody levels greater than three standard deviations above the mean levels of a pool of malaria naïve sera). We described the dynamics of antibody responses to these antigens by identifying factors predictive of antibody levels using linear regression models.ResultsOf the 25 antigens selected, seven antigens were produced successfully as recombinant proteins, with one variant antigen, giving a total of eight proteins for evaluation. Antibodies to the candidate antigens were detectable in the study population (N = 216), with seroprevalence ranging from 37.0% (95% CI: 30.6%, 43.9%) for PSOP1 to 77.8% (95% CI: 71.6%, 83.1%) for G377 (3D7 variant). Responses to AMA1 and GE were more prevalent than those to the gametocyte proteins at 87.9% (95% CI: 82.8%, 91.9%) and 88.3% (95% CI: 83.1%, 92.4%), respectively. Additionally, both antibody levels and breadth of antibody responses were associated with age and concurrent parasitaemia.ConclusionAge and concurrent parasitaemia remain important determinants of naturally acquired immunity to gametocyte antigens. Furthermore, we identify novel candidates for transmission-blocking activity evaluation.

scholarly journals Effects of heterogeneity in infection-exposure history and immunity on the dynamics of a protozoan parasite

2007 ◽  
Vol 4 (16) ◽  
pp. 841-849 ◽  
Author(s):  
Maite Severins ◽  
Don Klinkenberg ◽  
Hans Heesterbeek
Keyword(s):  
Dynamic Behaviour ◽  
Protozoan Parasite ◽  
Host Population ◽  
Infection Process ◽  
Control Measures ◽  
Complex Dynamic ◽  
Systems Models ◽  
Exposure History ◽  
The Relationship ◽  
Initial Contamination

Infection systems where traits of the host, such as acquired immunity, interact with the infection process can show complex dynamic behaviour with counter-intuitive results. In this study, we consider the traits ‘immune status’ and ‘exposure history’, and our aim is to assess the influence of acquired individual heterogeneity in these traits. We have built an individual-based model of Eimeria acervulina infections, a protozoan parasite with an environmental stage that causes coccidiosis in chickens. With the model, we simulate outbreaks of the disease under varying initial contaminations. Heterogeneity in the traits arises stochastically through differences in the dose and frequency of parasites that individuals pick up from the environment. We find that the relationship between the initial contamination and the severity of an outbreak has a non-monotonous ‘wave-like’ pattern. This pattern can be explained by an increased heterogeneity in the host population caused by the infection process at the most severe outbreaks. We conclude that when dealing with these types of infection systems, models that are used to develop or evaluate control measures cannot neglect acquired heterogeneity in the host population traits that interact with the infection process.

scholarly journals Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 627
Author(s):  
Sławomir Letkiewicz ◽  
Marzanna Łusiak-Szelachowska ◽  
Ryszard Międzybrodzki ◽  
Maciej Żaczek ◽  
Beata Weber-Dąbrowska ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Serum Antibody ◽  
Multidrug Resistant ◽  
Antibody Responses ◽  
Urogenital Infections ◽  
Reliable Model ◽  
Tract Infections ◽  
Antibody Levels

Patients with chronic urinary and urogenital multidrug resistant bacterial infections received phage therapy (PT) using intravesical or intravesical and intravaginal phage administration. A single course of PT did not induce significant serum antibody responses against administered phage. Whilst the second cycle of PT caused a significant increase in antibody levels, they nevertheless remained quite low. These data combined with good therapy results achieved in some patients suggest that this mode of PT may be an efficient means of therapy for urogenital infections and a reliable model for a clinical trial of PT.

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