The balance of cellular and humoral immunity determines the level of protection offered by an HIV vaccine in macaque models of HIV infection

2015 ◽  
Vol 06 (10) ◽  
Author(s):  
Timothy Fouts
2015 ◽  
Vol 112 (9) ◽  
pp. E992-E999 ◽  
Author(s):  
Timothy R. Fouts ◽  
Kenneth Bagley ◽  
Ilia J. Prado ◽  
Kathryn L. Bobb ◽  
Jennifer A. Schwartz ◽  
...  

A guiding principle for HIV vaccine design has been that cellular and humoral immunity work together to provide the strongest degree of efficacy. However, three efficacy trials of Ad5-vectored HIV vaccines showed no protection. Transmission was increased in two of the trials, suggesting that this vaccine strategy elicited CD4+ T-cell responses that provide more targets for infection, attenuating protection or increasing transmission. The degree to which this problem extends to other HIV vaccine candidates is not known. Here, we show that a gp120-CD4 chimeric subunit protein vaccine (full-length single chain) elicits heterologous protection against simian-human immunodeficiency virus (SHIV) or simian immunodeficiency virus (SIV) acquisition in three independent rhesus macaque repeated low-dose rectal challenge studies with SHIV162P3 or SIVmac251. Protection against acquisition was observed with multiple formulations and challenges. In each study, protection correlated with antibody-dependent cellular cytotoxicity specific for CD4-induced epitopes, provided that the concurrent antivaccine T-cell responses were minimal. Protection was lost in instances when T-cell responses were high or when the requisite antibody titers had declined. Our studies suggest that balance between a protective antibody response and antigen-specific T-cell activation is the critical element to vaccine-mediated protection against HIV. Achieving and sustaining such a balance, while enhancing antibody durability, is the major challenge for HIV vaccine development, regardless of the immunogen or vaccine formulation.


Author(s):  
Inga N. Alikina ◽  
Olga A. Kazakova

Introduction. Studies indicate the high pathogenetic significance of the immune component in the development of atherosclerosis. The aim of the study is a comparative assessment of immunological parameters in workers of petrochemical production with varying degrees of imbalance in lipid metabolism and the development of the atherosclerotic process. Materials and methods. Men working at an oil production enterprise in the Perm Region were examined. The observation group consisted of oil production operators with a diagnosis of atherosclerosis, the comparison group - with dyslipidemia syndrome. To determine the parameters of lipid metabolism, the results of a biochemical blood test were used. CD-immunogram parameters were identified by flow cytometry. Specific antibodies to benzene were determined by the allergosorbent method. Results. The results of a comparative study of fat metabolism confirmed violations of the physiological ratio of lipids in the blood of oil production workers, which were expressed in a significant imbalance in the levels of lipidogram. There was an increased level of specific IgG antibodies to benzene in the observation group in relation to the comparison group. An imbalance of cellular immunity was found, which was characterized by signs of indicators activation of cellular differentiation clusters. Conclusions. Studies of immune system compartments demonstrate excessive activation of cellular and humoral immunity in oil production workers under the influence of a combination of harmful production factors. The simultaneously formed imbalance of lipid metabolism is associated with various degrees of clinical manifestation of atherosclerotic disorders, with the influence of harmful production factors, aggressiveness of cellular and humoral immunity, and smoking.


Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 298
Author(s):  
Daniele Focosi ◽  
Angelo Genoni ◽  
Ersilia Lucenteforte ◽  
Silvia Tillati ◽  
Antonio Tamborini ◽  
...  

Antibody-dependent enhancement (ADE) of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection has been hypothesized. However, to date, there has been no in vitro or in vivo evidence supporting this. Cross-reactivity exists between SARS CoV-2 and other Coronaviridae for both cellular and humoral immunity. We show here that IgG against nucleocapsid protein of alphacoronavirus NL63 and 229E correlate with the World Health Organization’s (WHO) clinical severity score ≥ 5 (incidence rate ratios was 1.87 and 1.80, respectively, and 1.94 for the combination). These laboratory findings suggest possible ADE of SARS CoV-2 infection by previous alphacoronavirus immunity.


npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Hyundong Jo ◽  
Bong Yoon Kim ◽  
So Hui Park ◽  
Hyun Mi Kim ◽  
Sung Ho Shin ◽  
...  

AbstractCurrent foot-and-mouth disease (FMD) vaccines have significant limitations, including side effects due to oil emulsions at the vaccination site, a narrow spectrum of protective efficacy, and incomplete host defenses mediated by humoral immunity alone. To overcome these limitations, new FMD vaccines must ensure improved safety with non-oil-based adjuvants, a broad spectrum of host defenses within/between serotypes, and the simultaneous induction of cellular and humoral immunity. We designed a novel, immune-potent, recombinant protein rpHSP70-AD that induces robust cellular immunity and elicits a broad spectrum of host defenses against FMD virus (FMDV) infections. We demonstrated that an oil emulsion-free vaccine containing rpHSP70-AD mediates early, mid-term, and long-term immunity and drives potent host protection against FMDV type O and A, suggesting its potential as an FMD vaccine adjuvant in mice and pigs. These results suggest a key strategy for establishing next-generation FMD vaccines, including novel adjuvants.


2015 ◽  
Vol 23 (2) ◽  
pp. 84-94 ◽  
Author(s):  
David R. Martinez ◽  
Sallie R. Permar ◽  
Genevieve G. Fouda

ABSTRACTExtensive studies have demonstrated that infant immune responses are distinct from those of adults. Despite these differences, infant immunization can elicit protective immune responses at levels comparable to or, in some cases, higher than adult immune responses to many vaccines. To date, only a few HIV vaccine candidates have been tested in infant populations, and none of them evaluated vaccine efficacy. Recent exciting studies showing that HIV-infected infants can develop broad neutralizing antibody responses and that some HIV vaccine regimens can elicit high levels of potentially protective antibodies in infants provide support for the development and testing of HIV vaccines in pediatric populations. In this review, we discuss the differences in adult and infant immune responses in the setting of HIV infection and vaccination.


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