One mouse was lost in the group (V/N) at 21 days. improved the induction of HIV-1 Env-specific humoral and cellular immune responses compared to homologous prime/boost protocols. Specifically, the combination of VSV-GP in the primary and NYVAC in the boost induced higher HIV-1 Env-specific T cell (CD4/CD8 T cells and T follicular helper -Tfh- cells) immune responses compared to the use of DNA or NYVAC vectors in the primary and VSV-GP in the boost. Such enhanced T cell responses correlated with an enhancement of the Env-specific germinal center (GC) B cell populace and with a greatly biased Env-specific response toward the Th1-associated IgG2a and IgG3 subclasses, while the other groups showed a Th2-associated IgG1 bias. In summary, our T and B cell populace data exhibited that VSV-GP-based vectors could be taken into consideration as an optimized immunogenic HIV-1 vaccine candidate component against HIV-1 when utilized for priming in heterologous combinations with the poxvirus vector NYVAC as a boost. Keywords: HIV-1 Env, vaccine, VSV-GP, NYVAC, mice immunization, T and B cells, antibodies, immune correlates Introduction Since the discovery of the Human Immunodeficiency Computer virus type 1 (HIV-1) as the causal agent of Acquired Immunodeficiency Syndrome (AIDS) in 1983 (1), many efforts have been performed to discontinue the HIV/AIDS pandemic. The latest estimate indicates that 37.9 million people were living with HIV/AIDS worldwide at the end of 2018 and 770.000 persons died of AIDS Alizapride HCl in 2018, with sub-Saharan Africa continuing the Alizapride HCl region most severely affected by the HIV/AIDS pandemic (http://www.unaids.org/en). A significant success in the HIV field has been the development of the life-saving combined antiretroviral therapy (cART) able to suppress the plasma viremia and reduce the risk of HIV-1 transmission (2) and its accessibility to an increasing number of people worldwide. However, the presence of latent HIV-1 reservoirs makes the complete elimination of the computer virus in cART-treated infected individuals remarkably hard (3, 4). Therefore, a safe and effective vaccine able to prevent and eliminate the HIV/AIDS pandemic is usually required but still missing. To date, only one HIV-1 phase III clinical trial (Thai RV144 trial) has reported some efficacy (31.2%) against HIV-1 acquisition (5). At present, the evaluation of the vaccine-induced immune correlates of protection in non-human primates (NHPs) and in humans, such as broadly neutralizing antibodies (bNAbs), non-neutralizing antibodies targeting the variable loops 1 and 2 (V1/V2) of the HIV-1 envelope (Env), Env-specific polyfunctional antibodies and T cell responses, are guiding different HIV-1 vaccine methods and regimens (6C8). The RV144 regimen, novel vaccines based on adenovirus vectors, mosaic immunogens, optimized gp140 proteins (such as HIV-1 Env SOSIP trimers) and passive administration of monoclonal antibodies are among the most recent strategies for HIV-1 prevention and treatment. Since the main objective in the HIV-1 vaccine field is usually to establish immunization protocols that elicit protective HIV-1-specific responses through the induction of bNAbs together with potent T cell activation, major efforts have been directed to determine the best-in-class Rabbit Polyclonal to MPRA combination of both preventive and therapeutic vaccine candidates in preclinical and clinical trials (9C12). The most advanced phase IIb prophylactic clinical studies underway involved the combination of the poxvirus ALVAC vector plus the gp120 protein component (HVTN 702 study; https://www.clinicaltrials.gov/ct2/show/NCT02968849), as well as an adenovirus vector plus the gp140 protein component (HVTN 705/HPX2008 study; https://www.clinicaltrials.gov/ct2/show/NCT03060629). It has to be decided whether these trials will accomplish the desired efficacy. The recent promising success of ebola epidemic control using a VSV recombinant vector expressing the glycoprotein (GP) of the Zaire strain of ebola computer virus (13) has Alizapride HCl elevated the interest in this viral vector. We have recently Alizapride HCl explained a chimeric VSV vector in which the glycoprotein G of VSV has been Alizapride HCl replaced by the glycoprotein GP of the lymphocytic choriomeningitis computer virus (LCMV) (VSV-GP) as HIV-1 vaccine vector expressing different forms of HIV-1 Env that induced HIV-1-specific antibodies in mice and rabbits after repeated immunizations with VSV-based recombinant vectors (14). In addition, we have also explained in preclinical and clinical trials that primary/boost combinations of a poxvirus vector NYVAC with DNA and Env protein components induced broad HIV-1-specific T and B cell responses (15C18). Both in NHPs and human clinical trials the DNA/NYVAC/protein immunization.