B lymphocytes in COVID-19: a tale of harmony and discordance.

B lymphocytes play a vital role in the human defense against viral infections by producing specific antibodies. They are also critical for the prevention of infectious diseases by vaccination, and their activation influences the efficacy of the vaccination. Since the beginning of coronavirus disease 2019 (COVID-19), which became the main concern of the world health system, many efforts have been made to treat and prevent the disease. However, for the development of successful therapeutics and vaccines, it is necessary to understand the interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, and the immune system. The innate immune system provides primary and nonspecific defense against the virus, but within several days after infection, a virus-specific immune response is provided first by antibody-producing B cells, which are converted after the resolution of disease to memory B cells, which provide long-term immunity. Although a failure in B cell activation or B cell dysfunction can cause a severe form of the disease and also lead to vaccination inefficiency, some individuals with B cell immunodeficiency have shown less production of the cytokine IL-6, resulting in a better disease outcome. In this review, we present the latest findings on the interaction between SARS-CoV-2 and B lymphocytes during COVID-19 infection.

An HIV stochastic model with cell-to-cell infection, B-cell immune response and distributed delay.

In this study, a delayed HIV stochastic model with virus-to-cell infection, cell-to-cell transmission and B-cell immune response is proposed. We first transform the stochastic differential equation with distributed delay into a high-dimensional degenerate stochastic differential equation, and then theoretically analyze the dynamic behaviour of the degenerate model. The unique global solution of the model is given by rigorous analysis. By formulating suitable Lyapunov functions, the existence of the stationary Markov process is obtained if the stochastic B-cell-activated reproduction number is greater than one. We also use the law of large numbers theorem and the spectral radius analysis method to deduce that the virus can be cleared if the stochastic B-cell-inactivated reproduction number is less than one. Through uncertainty and sensitivity analysis, we obtain key parameters that determine the value of the stochastic B-cell-activated reproduction number. Numerically, we examine that low level noise can maintain the number of the virus and B-cell populations at a certain range, while high level noise is helpful for the elimination of the virus. Furthermore, the effect of the cell-to-cell infection on model behaviour, and the influence of the key parameters on the size of the stochastic B-cell-activated reproduction number are also investigated.

The Role of Nucleoprotein in Immunity to Human Negative-Stranded RNA Viruses-Not Just Another Brick in the Viral Nucleocapsid.

Negative-stranded RNA viruses (NSVs) are important human pathogens, including emerging and reemerging viruses that cause respiratory, hemorrhagic and other severe illnesses. Vaccine design traditionally relies on the viral surface glycoproteins. However, surface glycoproteins rarely elicit effective long-term immunity due to high variability. Therefore, an alternative approach is to include conserved structural proteins such as nucleoprotein (NP). NP is engaged in myriad processes in the viral life cycle: coating and protection of viral RNA, regulation of transcription/replication processes and induction of immunosuppression of the host. A broad heterosubtypic T-cellular protection was ascribed very early to this protein. In contrast, the understanding of the humoral immunity to NP is very limited in spite of the high titer of non-neutralizing NP-specific antibodies raised upon natural infection or immunization. In this review, the data with important implications for the understanding of the role of NP in the immune response to human NSVs are revisited. Major implications of the elicited T-cell immune responses to NP are evaluated, and the possible multiple mechanisms of the neglected humoral response to NP are discussed. The intention of this review is to remind that NP is a very promising target for the development of future vaccines.

Viral dynamics of a latent HIV infection model with Beddington-DeAngelis incidence function, B-cell immune response and multiple delays.

In this paper, an HIV infection model with latent infection, Beddington-DeAngelis infection function, B-cell immune response and four time delays is formulated. The well-posedness of the model solution is rigorously derived, and the basic reproduction number $\mathcal{R}_0$ and the B-cell immune response reproduction number $\mathcal{R}_1$ are also obtained. By analyzing the modulus of the characteristic equation and constructing suitable Lyapunov functions, we establish the global asymptotic stability of the uninfected and the B-cell-inactivated equilibria for the four time delays, respectively. Hopf bifurcation occurs at the B-cell-activated equilibrium when the model includes the immune delay, and the B-cell-activated equilibrium is globally asymptotically stable if the model does not include it. Numerical simulations indicate that the increase of the latency delay, the cell infection delay and the virus maturation delay can cause the B-cell-activated equilibrium stabilize, while the increase of the immune delay can cause it destabilize.

Immune Modulation of NYVAC-Based HIV Vaccines by Combined Deletion of Viral Genes that Act on Several Signalling Pathways.

An HIV-1 vaccine continues to be a major target to halt the AIDS pandemic. The limited efficacy of the RV144 phase III clinical trial with the canarypox virus-based vector ALVAC and a gp120 protein component led to the conclusion that improved immune responses to HIV antigens are needed for a more effective vaccine. In non-human primates, the New York vaccinia virus (NYVAC) poxvirus vector has a broader immunogenicity profile than ALVAC and has been tested in clinical trials. We therefore analysed the HIV immune advantage of NYVAC after removing viral genes that act on several signalling pathways (Toll-like receptors-TLR-interferon, cytokines/chemokines), as well as genes of unknown immune function. We generated a series of NYVAC deletion mutants and studied immune behaviour (T and B cell) to HIV antigens and to the NYVAC vector in mice. Our results showed that combined deletion of selected vaccinia virus (VACV) genes is a valuable strategy for improving the immunogenicity of NYVAC-based vaccine candidates. These immune responses were differentially modulated, positive or negative, depending on the combination of gene deletions. The deletions also led to enhanced antigen- or vector-specific cellular and humoral responses. These findings will facilitate the development of optimal NYVAC-based vaccines for HIV and other diseases.

Humoral and B-cell memory responses in children five years after pertussis acellular vaccine priming.

The resurgence of pertussis suggests the need for greater efforts in understanding the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of humoral and B-cell memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac(®) vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa(®) (Infanrix) (GlaxoSmithKline Biologicals). We evaluated the specific immune responses in the two groups of children, 5 years after primary vaccination by measuring the persistence of IgG and antibody secreting cells (ASC) specific for vaccine antigens. Part of the enrolled children received only primary vaccination, while others had the pre-school boost dose. A similar level of antigen-specific IgG and ASC was found in Infanrix and Hexavac vaccinated children. The mean IgG levels were significantly higher in children that received the pre-school boost as compared with children that did not receive the boost dose. A longer persistence after the pre-school boost of IgG-Pertussis Toxin (PT) and IgG-pertactin levels was observed in Infanrix primed children, but it was not statistically significant. More than 80% of children presented a positive ASC B memory response. Around 50% of children still presented protective IgG-PT levels which are reduced to 36% in no-boosted children. The pre-school booster dose restores the percentage of protected children above 50%. In conclusion our data underline the importance of giving a booster dose 5 years after primary vaccination and suggest the need for a new vaccine able to induce a long lasting protective response.