scholarly journals Magnitude, specificity and avidity of sporozoite specific antibodies associate with protection status and distinguish among RTS,S/AS01 dose regimens

2020 ◽  
Author(s):  
S Moses Dennison ◽  
Matthew Reichartz ◽  
Milite Abraha ◽  
Rachel L Spreng ◽  
Ulrike Wille-Reece ◽  
...  
Keyword(s):  
Malaria Vaccine ◽  
Specific Binding ◽  
Standard Dose ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Fractional Dose ◽  
Controlled Human Malaria Infection ◽  
Binding Antibody ◽  
Antibody Dynamics ◽  
Sporozoite Infection

Abstract Background The malaria vaccine, RTS,S/AS01, demonstrated an enhanced efficacy (86.7%) in a delayed third fractional dose (0.1.7Fx) regimen in controlled human malaria infection (CHMI) trials compared to a standard full dose (0.1.2) regimen (62.5%). In order to understand the humoral component of the RTS,S/AS01 vaccine-induced protection against sporozoite infection in these two regimens, we investigated the serum antibody dynamics of 0.1.2 and 0.1.7Fx groups vaccinees. Methods The specific binding responses (magnitude) and dissociation rates (avidity) of serum antibodies interaction with a recombinant Plasmodium falciparum circumsporozoite protein (CSP) and peptides corresponding to the central repeat region (NANP6), the C-terminal region (PF16) and the N-terminal junction (N-interface) of CSP, respectively, were measured using a Biolayer Interferometry (BLI) assay. Results On the day of challenge, higher NANP6 specific antibody responses were associated with protection in the 0.1.2 group. Contrarily, slower antibody dissociation rates for CSP and PF16 binding were observed in the protected 0.1.7Fx group. Protected vaccinees of both groups exhibited 2 to 3-fold higher N-interface peptide binding antibody responses. Conclusions Unlike the standard dose, the delayed-fractional third dose of RTS,S/AS01 induced higher avidity CSP and PF16 binding antibodies that were associated with protection against sporozoite infection. Clinical Trials registration NCT01857869

scholarly journals Estimation of Seasonal Influenza Attack Rates and Antibody Dynamics in Children Using Cross-Sectional Serological Data

2020 ◽  
Author(s):  
Amanda Minter ◽  
Katja Hoschler ◽  
Ya Jankey Jagne ◽  
Hadijatou Sallah ◽  
Edwin Armitage ◽  
...  
Keyword(s):  
Bayesian Model ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Sub Saharan Africa ◽  
Cross Sectional ◽  
Sub Saharan ◽  
Serological Data ◽  
Antibody Dynamics

Abstract Directly measuring evidence of influenza infections is difficult, especially in low-surveillance settings such as sub-Saharan Africa. Using a Bayesian model, we estimated unobserved infection times and underlying antibody responses to influenza A/H3N2, using cross-sectional serum antibody responses to 4 strains in children aged 24–60 months. Among the 242 individuals, we estimated a variable seasonal attack rate and found that most children had ≥1 infection before 2 years of age. Our results are consistent with previously published high attack rates in children. The modeling approach highlights how cross-sectional serological data can be used to estimate epidemiological dynamics.

scholarly journals Pre-existing antibodies targeting a dominant linear antibody epitope on SARS-CoV-2 S2 cross-reacted with commensal gut bacteria and shaped immune responses elicited by a candidate vaccine

2021 ◽  
Author(s):  
Liqiu Jia ◽  
Shufeng Weng ◽  
Jing Wu ◽  
Xiangxiang Tian ◽  
Yifan Zhang ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Specific Binding ◽  
Gut Bacteria ◽  
Antibody Responses ◽  
Spike Protein ◽  
Linear Epitope ◽  
Healthy Human ◽  
Antibody Epitope ◽  
Binding Antibody ◽  
Low Levels

Pre-existing SARS-CoV-2 cross-reactive antibodies have been detected in both unexposed human and animals. However, the origins of these cross-reactive antibodies and their potential impacts on vaccine efficacy have not been completely clarified. In this study, we demonstrated that the S2 subunit was the predominant target of the pre-existing SARS-CoV-2 spike protein cross-reactive antibodies in both healthy human and naive SPF mice. Through linear epitope mapping, we identified a dominant antibody epitope on the connector domain of S2 (aa1145-aa1162), which could be recognized by antibodies pre-existed in unexposed human and mice. Six monoclonal antibodies against this linear epitope were isolated from naive SPF mice and were proved to cross-react with commensal gut bacteria collected from both human and mouse. Via immunizing mice with a candidate DNA vaccine encoding the full length of SARS-CoV-2 spike protein, we further demonstrated that high levels of pre-existing S2 cross-reactive antibodies did not impair the immunogenicity of the DNA vaccine. On the contrary, mice with high levels of pre-existing antibodies mounted stronger S2 specific binding antibody responses compared to mice with low levels of pre-existing antibodies. In addition, S1 specific T cell and binding antibody responses also tended to be enhanced in mice with high levels of pre-existing antibodies.

scholarly journals A delayed fractionated dose RTS,S AS01 vaccine regimen mediates protection via improved T follicular helper and B cell responses

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Suresh Pallikkuth ◽  
Sidhartha Chaudhury ◽  
Pinyi Lu ◽  
Li Pan ◽  
Erik Jongert ◽  
...  
Keyword(s):  
B Cell ◽  
Malaria Vaccine ◽  
Vaccine Dose ◽  
Cell Responses ◽  
The Third ◽  
Follicular Helper ◽  
Specific Memory ◽  
Fractional Dose ◽  
Controlled Human Malaria Infection ◽  
B Cell Responses

Malaria-071, a controlled human malaria infection trial, demonstrated that administration of three doses of RTS,S/AS01 malaria vaccine given at one-month intervals was inferior to a delayed fractional dose (DFD) schedule (62.5% vs 86.7% protection, respectively). To investigate the underlying immunologic mechanism, we analyzed the B and T peripheral follicular helper cell (pTfh) responses. Here, we show that protection in both study arms was associated with early induction of functional IL-21-secreting circumsporozoite (CSP)-specific pTfh cells, together with induction of CSP-specific memory B cell responses after the second dose that persisted after the third dose. Data integration of key immunologic measures identified a subset of non-protected individuals in the standard (STD) vaccine arm who lost prior protective B cell responses after receiving the third vaccine dose. We conclude that the DFD regimen favors persistence of functional B cells after the third dose.

scholarly journals Waning antibody responses in COVID-19: what can we learn from the analysis of other coronaviruses?

Infection ◽  
2021 ◽  
Author(s):  
Ali Hamady ◽  
JinJu Lee ◽  
Zuzanna A. Loboda
Keyword(s):  
Cross Reactivity ◽  
Antibody Responses ◽  
The Novel ◽  
Incidence And Mortality ◽  
Antibody Titres ◽  
Human Coronaviruses ◽  
Public Health Strategies ◽  
Antibody Dynamics

Abstract Objectives The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due to the continuing surge in incidence and mortality globally, determining whether protective, long-term immunity develops after initial infection or vaccination has become critical. Methods/Results In this narrative review, we evaluate the latest understanding of antibody-mediated immunity to SARS-CoV-2 and to other coronaviruses (SARS-CoV, Middle East respiratory syndrome coronavirus and the four endemic human coronaviruses) in order to predict the consequences of antibody waning on long-term immunity against SARS-CoV-2. We summarise their antibody dynamics, including the potential effects of cross-reactivity and antibody waning on vaccination and other public health strategies. At present, based on our comparison with other coronaviruses we estimate that natural antibody-mediated protection for SARS-CoV-2 is likely to last for 1–2 years and therefore, if vaccine-induced antibodies follow a similar course, booster doses may be required. However, other factors such as memory B- and T-cells and new viral strains will also affect the duration of both natural and vaccine-mediated immunity. Conclusion Overall, antibody titres required for protection are yet to be established and inaccuracies of serological methods may be affecting this. We expect that with standardisation of serological testing and studies with longer follow-up, the implications of antibody waning will become clearer.

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.

scholarly journals Induction of Mucosal Protection against Primary, Heterologous Simian Immunodeficiency Virus by a DNA Vaccine

2002 ◽  
Vol 76 (7) ◽  
pp. 3309-3317 ◽  
Author(s):  
Deborah Heydenburg Fuller ◽  
Premeela A. Rajakumar ◽  
Lawrence A. Wilson ◽  
Anita M. Trichel ◽  
James T. Fuller ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Dna Vaccine ◽  
Dna Sequences ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Effective Vaccine ◽  
Lymphoid Tissues ◽  
Mucosal Protection ◽  
Mucosal Transmission ◽  
Immunodeficiency Virus

ABSTRACT An effective vaccine against human immunodeficiency virus (HIV) should protect against mucosal transmission of genetically divergent isolates. As a safe alternative to live attenuated vaccines, the immunogenicity and protective efficacy of a DNA vaccine containing simian immunodeficiency virus (SIV) strain 17E-Fr (SIV/17E-Fr) gag-pol-env was analyzed in rhesus macaques. Significant levels of cytotoxic T lymphocytes (CTL), but low to undetectable serum antibody responses, were observed following multiple immunizations. SIV-specific mucosal antibodies and CTL were also detected in rectal washes and gut-associated lymphoid tissues, respectively. Vaccinated and naive control monkeys were challenged intrarectally with SIV strain DeltaB670 (SIV/DeltaB670), a primary isolate whose env is 15% dissimilar to that of the vaccine strain. Four of seven vaccinees were protected from infection as determined by the inability to identify viral RNA or DNA sequences in the peripheral blood and the absence of anamnestic antibody responses postchallenge. This is the first report of mucosal protection against a primary pathogenic, heterologous isolate of SIV by using a commercially viable vaccine approach. These results support further development of a DNA vaccine for protection against HIV.

scholarly journals Serum Antibody Responses after Intradermal Injection of Influenza Vaccine

2005 ◽  
Vol 2 (1) ◽  
pp. 35-38
Author(s):  
Maliheh Metanat ◽  
Masoud Salehi . ◽  
Batool Sharifi-Mood . ◽  
Mohammad-Reza Safai .
Keyword(s):  
Influenza Vaccine ◽  
Serum Antibody ◽  
Intradermal Injection ◽  
Antibody Responses

scholarly journals Expansion of Functional Myeloid-Derived Suppressor Cells in Controlled Human Malaria Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Carlos Lamsfus Calle ◽  
Rolf Fendel ◽  
Anurag Singh ◽  
Thomas L. Richie ◽  
Stephen L. Hoffman ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Malaria Infection ◽  
Malaria Vaccine ◽  
Suppressor Cells ◽  
T Cell Proliferation ◽  
Myeloid Derived Suppressor Cells ◽  
Controlled Human Malaria Infection

Malaria can cause life-threatening complications which are often associated with inflammatory reactions. More subtle, but also contributing to the burden of disease are chronic, often subclinical infections, which result in conditions like anemia and immunologic hyporesponsiveness. Although very frequent, such infections are difficult to study in endemic regions because of interaction with concurrent infections and immune responses. In particular, knowledge about mechanisms of malaria-induced immunosuppression is scarce. We measured circulating immune cells by cytometry in healthy, malaria-naïve, adult volunteers undergoing controlled human malaria infection (CHMI) with a focus on potentially immunosuppressive cells. Infectious Plasmodium falciparum (Pf) sporozoites (SPZ) (PfSPZ Challenge) were inoculated during two independent studies to assess malaria vaccine efficacy. Volunteers were followed daily until parasites were detected in the circulation by RT-qPCR. This allowed us to analyze immune responses during pre-patency and at very low parasite densities in malaria-naïve healthy adults. We observed a consistent increase in circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in volunteers who developed P. falciparum blood stage parasitemia. The increase was independent of preceding vaccination with a pre-erythrocytic malaria vaccine. PMN-MDSC were functional, they suppressed CD4+ and CD8+ T cell proliferation as shown by ex-vivo co-cultivation with stimulated T cells. PMN-MDSC reduced T cell proliferation upon stimulation by about 50%. Interestingly, high circulating PMN-MDSC numbers were associated with lymphocytopenia. The number of circulating regulatory T cells (Treg) and monocytic MDSC (M-MDSC) showed no significant parasitemia-dependent variation. These results highlight PMN-MDSC in the peripheral circulation as an early indicator of infection during malaria. They suppress CD4+ and CD8+ T cell proliferation in vitro. Their contribution to immunosuppression in vivo in subclinical and uncomplicated malaria will be the subject of further research. Pre-emptive antimalarial pre-treatment of vaccinees to reverse malaria-associated PMN-MDSC immunosuppression could improve vaccine response in exposed individuals.

scholarly journals Immunoprofiles associated with controlled human malaria infection and naturally acquired immunity identify a shared IgA pre-erythrocytic immunoproteome

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Andrea A. Berry ◽  
Joshua M. Obiero ◽  
Mark A. Travassos ◽  
Amed Ouattara ◽  
Drissa Coulibaly ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Vaccine Development ◽  
Protein Microarray ◽  
Antibody Responses ◽  
Liver Stage ◽  
Human Malaria ◽  
Controlled Human Malaria Infection ◽  
Iga Antibody ◽  
Potential Vaccine ◽  
Antigen Protein

AbstractKnowledge of the Plasmodium falciparum antigens that comprise the human liver stage immunoproteome is important for pre-erythrocytic vaccine development, but, compared with the erythrocytic stage immunoproteome, more challenging to classify. Previous studies of P. falciparum antibody responses report IgG and rarely IgA responses. We assessed IgG and IgA antibody responses in adult sera collected during two controlled human malaria infection (CHMI) studies in malaria-naïve volunteers and in 1- to 6-year-old malaria-exposed Malian children on a 251 P. falciparum antigen protein microarray. IgG profiles in the two CHMI groups were equivalent and differed from Malian children. IgA profiles were robust in the CHMI groups and a subset of Malian children. We describe immunoproteome differences in naïve vs. exposed individuals and report pre-erythrocytic proteins recognized by the immune system. IgA responses detected in this study expand the list of pre-erythrocytic antigens for further characterization as potential vaccine candidates.

Sign in / Sign up

Export Citation Format

Share Document