Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles

The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes.

Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles

The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically-relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display have been modest for Env trimers. Here, we generated two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. An immunization study in rabbits demonstrated that these nanoparticles induced 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping revealed that nanoparticle presentation focused antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes.

Knowledge, Attitude and Practices of Pregnant Women regarding Benefits of Breast Feeding and Immunization in newborns.

Objectives: To study the knowledge attitude and practices of pregnant women regarding benefits of breastfeeding and immunization. Study design: Descriptive cross-sectional study Material and Method: This study was conducted at Department of Obstetrics of P.N.S. Shifa Hospital Karachi over a period of six months. All pregnant women admitted in the obstetric ward were included. After obtaining informed consent participants were administered questionnaire, which was filled in by the researcher. The questions were in the native language. Performa includes questions pertinent to knowledge, attitude and practices regarding benefits of breast feeding and immunization to achieve the millennium development goal 4. Results: Despite of the level of education out of 235 participants at most of them (97%) were aware of role of immunization and breast feeding. But 14.5% lack knowledge of frequency of breast feeding. 42.11% participants said doctor advise her to breast feed while 52.2% counseled by the family lady, midwife and friends. 45.96% participants never got advice by the doctors against use of un-prescribed drugs during pregnancy. Conclusion: The knowledge attitude and practices of pregnant women regarding benefits of breastfeeding and immunization are not upto the mark. There is a need to increase the education of the mothers to ensure better understanding regarding breastfeeding and immunization to achieve the Millennium Development Goal 4.

An HIV Envelope gp120-Fc Fusion Protein Elicits Effector Antibody Responses in Rhesus Macaques

ABSTRACT A goal for HIV prevention programs is to develop safe, effective vaccines that elicit durable and broadly protective antibodies. Many vaccine programs focus on the immune responses to critical epitopes in the gp120 portion of HIV envelope glycoprotein (Env) and seek to improve the quality and quantity of antibodies by altering the sequence, conformation, oligomerization, or glycosylation of gp120 to activate appropriate germ line B cells and mimic the subsequent maturation pathways seen in infected individuals. As a complement to these strategies, we developed dimeric fusion protein immunogens consisting of HIVBaL gp120 monomer attached to a Gly/Ser linker that is, in turn, fused to one half of the dimeric Fc domain from rhesus macaque IgG1 (Env-rFc). We envisioned that Env-rFc may mimic some aspects of immune complexes by binding Fc gamma receptors (FcγRs) on immune cells to increase the strength, breadth, and durability of Env-specific antibody responses. The Env-rFc retained a capacity to bind both cell surface CD4 and FcγRs. In a rhesus macaque immunization study, Env-rFc elicited higher gp120 binding antibody titers than Env and elicited antibodies that recognize CD4-induced epitopes. Env-rFc also induced antibodies capable of neutralizing tier 1A HIV pseudotyped viruses and mediating antibody-dependent cellular cytotoxicity, outcomes not observed with monomeric gp120 in our study. Serum antibodies produced in Env-rFc-immunized macaques had increased durability compared to that of Env monomer immunization. Our work suggests that adding IgG1 Fc to Env-based immunogens may stimulate increased effector capacity in the immune sera and improve the protective serum antibody response.

Sero-surveillance and sero-monitoring of locally produced PPR vaccine in the field and experimental level

Peste des Petits Ruminants (PPR) is a highly contagious, economically important viral disease of goats with high morbidity and mortality. To control the disease effectively a live attenuated vaccine is available in Bangladesh which is produced by Livestock Research Institute (LRI), Mohakhali, Dhaka. The study was carried out to determine the immune status and immune response against PPR in field and experimental Black Bengal goats. Sero-surveillance of PPR was conducted by using c-ELISA in non-vaccinated 240 goats in Gazipur, Sirajgonj and Barisal. Out of the 240 goats tested, of which only 39 (20.31%) goats had positive level of PPR antibodies while 16.25% (13 out of 80 goats) in Gazipur, 28.75% (23 out of 80 goats) in Barisal and 3.75% ((3 out of 80 goats)) in Sirajgonj. In case of sero-monitoring of PPR, the result revealed that vaccinated goats from Rajshahi showed high positive result and have higher seroprevalence where 75% (60 out of 80 goats) were seropositive and only 25% (20 out of 80 goats) are seronegative. These result indicated that vaccinated Rajshahi goats is more resistant for PPR virus than non vaccinated goats. In experimentally to perform sero-monitoring, 10 seronegative goats were selected and divided into two equal groups (A and B).The immunization study against PPR with a commercial PPR vaccine was conducted on 5 goats of group A by inoculating @ 1.0 ml vaccine / animal subcutaneously and group B kept as non-vaccinated. The antibody titres against PPR in goats were determined at 0 day on vaccination and after 21DPV, 180DPV and 365DPV. The results found that 100% (5 out 5goats) seronegative in both vaccinated goats of group A and non-vaccinated goats of group B at 0 day on vaccination. The mean negative titres± SD were 79.285±13.921 and 76.707±9.265 in vaccinated group A and group B, respectively. The mean positive titers ±SD were 20.201±2.480, 8.630±4.970 and 11.382±1.419 at 21DPV, 180DPV an 365DPV, respectively in group A (100% seropositive). In case of non-vaccinated group B, the mean negative titres±SD were 74.258±7.793, 77.726±9.142 and 82.965±7.492 at 21DPV, 180DPV and 365DPV, respectively (100% seronegative). As it is observed, the antibody titres remain at the level over the period of time that indicates the immune response against PPR. From this finding, it is said that PPR vaccine could produce immune response in goats for about one year or 365 days.Asian J. Med. Biol. Res. March 2016, 2(1): 33-37

Factors related to missed opportunities for immunization at urban and suburban primary health centers in Medan

Background Missed opportunites for immunization is one of theimportant causes of low immunization coverage that should beprevented.Objective To investigate missed opportunities for immunizationand related factors at urban and suburban primary health centersin Medan.Methods A cross sectional study was conducted between January-March 2004. Primary health centers in Medan were divided intourban (20 primary health centers) and suburban (19 primaryhealth centers) groups. The sample size was 109 children whovisited primary health centers for immunization. Study was doneby a questionnaire taken after infants received immunization (exitinterview).Results The proportion of missed opportunities in urban andsuburban area was 22.3% (95% CI 16.9%;27.7%) and 29.9% (95%CI 24.0%;35.2%) (P=0.191), respectively. Factors such as age ofstarting immunization, number of children more than 4, and lowparental attitude about immunization (P=0.001) were related tomissed opportunities for immunization.Conclusions There is no difference between proportion of missedopportunities at primary health centers in urban and suburbanarea. Related factors to missed opportunities for immunizationare age of starting immunization older than 3 months, number ofchildren more than 4, and low parental attitude aboutimmunization.