Similarities between mucosa and blood antibodies in monkeys and the impact on vaccine development
A recent paper by Li et al., from the lab of Dan Barouch at Harvard shows very interesting results based on observations made from Rhesus macaques injected with experimental HIV vaccines. One of the key questions facing HIV vaccine researchers is whether one should design vaccine that stands a fair chance at inducing an immune response in the genital mucosa, since this is the portal of entry for the virus. The mucosal immune response is a key factor in vaccine efficacy and success against infection or disease progression.
This paper that appeared in Journal of Virology (doi: 10.1128/JVI.02095-14) first determined that the amount of IgG in serum was significantly higher than IgA whereas the amount of IgA in colorectal mucosal secretions was significantly higher than IgG. They also confirmed that IgA from mucosal secretions was largely secretory IgA and not serum contamination.
Next, they injected rhesus macaques with candidate HIV vaccines.
16 animals were injected (i.m.) with Adenovirus35 expressing SIVsme543-Env-Gag-Pol followed by Adenovirus26 expressing the same antigens at week 24.
8 animals were injected (i.m.) with 0.25 mg recombinant HIV-1 clade C CZA97.012 Env gp140 with adjuvant at weeks 0,4,8,12,16 and 20.
Both vaccines elicited high titres of Env-specific IgG and IgA in sera and mucosal secretions, even though mucosal antibody titres were much lower than that of serum.
To identify the subclasses of IgGs elicited, ELISAs were performed and while the Ad vectors elicited comparable tigers of IgG3 and IgG1 in sera and mucosal secretions. However, the protein vaccine elicited higher levels of IgG3 that IgG1.
Mucosal antibodies and serum antibodies neutralized TCLA strain SIV mac251.15 as compared to the sham group. Despite the overall predominance of IgA in mucosa, the sera and mucosal antibodies are functionally similar.
Using peptide microarrays that confer 57% of global HIV-1 Env sequences, it was found that the pattern of IgG binding to linear Env peptides were similar between serum and mucosal samples that largely bind V3 linear peptides followed by V1/V2 and V4 peptides. However, mucosal and serum IgG from protein-immunized monkeys showed binding to V1V2 region.
An interesting aspect of this paper is that protein immunization yielded a larger IgG3 response in the serum and mucosa. This corroborates with what has been uncovered from the RV144 trial where I have previously mentioned that IgG3 is the new kid on the block
This paper that appeared in Journal of Virology (doi: 10.1128/JVI.02095-14) first determined that the amount of IgG in serum was significantly higher than IgA whereas the amount of IgA in colorectal mucosal secretions was significantly higher than IgG. They also confirmed that IgA from mucosal secretions was largely secretory IgA and not serum contamination.
Next, they injected rhesus macaques with candidate HIV vaccines.
16 animals were injected (i.m.) with Adenovirus35 expressing SIVsme543-Env-Gag-Pol followed by Adenovirus26 expressing the same antigens at week 24.
8 animals were injected (i.m.) with 0.25 mg recombinant HIV-1 clade C CZA97.012 Env gp140 with adjuvant at weeks 0,4,8,12,16 and 20.
Both vaccines elicited high titres of Env-specific IgG and IgA in sera and mucosal secretions, even though mucosal antibody titres were much lower than that of serum.
To identify the subclasses of IgGs elicited, ELISAs were performed and while the Ad vectors elicited comparable tigers of IgG3 and IgG1 in sera and mucosal secretions. However, the protein vaccine elicited higher levels of IgG3 that IgG1.
Mucosal antibodies and serum antibodies neutralized TCLA strain SIV mac251.15 as compared to the sham group. Despite the overall predominance of IgA in mucosa, the sera and mucosal antibodies are functionally similar.
Using peptide microarrays that confer 57% of global HIV-1 Env sequences, it was found that the pattern of IgG binding to linear Env peptides were similar between serum and mucosal samples that largely bind V3 linear peptides followed by V1/V2 and V4 peptides. However, mucosal and serum IgG from protein-immunized monkeys showed binding to V1V2 region.
An interesting aspect of this paper is that protein immunization yielded a larger IgG3 response in the serum and mucosa. This corroborates with what has been uncovered from the RV144 trial where I have previously mentioned that IgG3 is the new kid on the block
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