Induction of Identical IgG HIV-1 Envelope Epitope Recognition Patterns After Initial HIVIS-DNA/MVA-CMDR Immunization and a Late MVA-CMDR Boost

Abstract

Joachim et al. HIV-1 Envelope Recognition in HIVIS03/06 Vaccinees 3 years effectively restored waned IgG responses to linear Env epitopes and induced targeting of identical antigenic regions and variants comparable to the previous combined HIVIS-DNA/MVA-CMDR regimen. Our findings support the notion that anti-HIV-1 Env responses, associated with a reduced risk of infection in RV144, could be maintained by regular boosting with a single dose of MVA-CMDR.

Stepwise Conformational Stabilization of a HIV-1 Clade C Consensus Envelope Trimer Immunogen Impacts the Profile of Vaccine-Induced Antibody Responses

“…Despite the limited antibody repertoire of mice, this observation is also in line with earlier peptide microarray analyses of clinical trials with Env-based immunogens conducted by us [ 38 , 39 , 40 , 43 ] and others [ 42 , 48 ]. Immunogens based on gp120 monomers such as those used in RV144 [ 42 ] and UKHVC003 [ 38 , 43 ] in general induced stronger and broader Env-specific IgG responses, targeting various antigenic regions on Env, while the membrane-tethered, more native-like trimeric proteins encoded by MVA-CMDR used in the HIVIS and TaMoVac trials [ 38 , 39 , 40 ] induced more focused and narrow antibody responses.…”

“…In addition to these, multiple other peptide variants were included for 15 previously identified immunodominant regions. These were identified in studies on different vaccine trials and natural HIV infection conducted by us and others [ 38 , 39 , 40 , 41 , 42 , 43 ]. Peptide variants covering these immunodominant regions in more depth with respect to the antigenic variation were selected as follows: All existing pre-seroconversion (n = 913) and recent (n = 723) HIV infection sequences from 192 subjects collected within 2010–2018 were obtained from the HIV database ( (accessed on 29 May 2018)).…”

“…These sequences were interrogated to identify the most frequently occurring molecular forms for the 15 selected Env regions. Moreover, peptide variants frequently identified in previous studies ([ 38 , 39 , 40 , 41 , 42 , 43 ] and unpublished data) are included to bridge newly generated data to results from these earlier studies. Peptides included in the microarray are representative of all HIV-1 clades, however, due to the focus on EHVA immunogens, Clade C is overrepresented.…”

“…Mouse sera were analyzed for the presence of HIV-1 Env-specific IgG antibodies as described before [ 40 ] with minor modifications. After blocking of the peptide microarray slides with blocking buffer (0.1% I-Block Protein-Based Blocking Reagent, Thermo Fisher Scientific, Waltham, MA, USA and 1 × ROTI Block, Carl Roth, Karlsruhe, Germany, in PBS), mouse sera were diluted 1:250 in blocking buffer and incubated for 2 h at RT.…”

Systems vaccinology analysis of a recombinant vaccinia-based vector reveals diverse innate immune signatures at the injection site

“…Recombinant poxvirus vector systems have a number of attractive features for vaccine development including a large payload capacity (at least 25,000 base pairs), potential for cold chain-independent distribution, lack of vaccine DNA integration and induction of both cellular and humoral immunity (Prow et al ., 2018a). Nevertheless, a range of strategies are being sought to improve immunogenicity and reduce reactogenicity (Albarnaz et al ., 2018; Chea et al ., 2019; Izzi et al ., 2014; Joachim et al ., 2020; Koch et al ., 2020; Marin et al ., 2018). Both these key characteristics of vaccines are largely dictated by the early behavior of the vaccine at the injection site.…”