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The Number and Complexity of Pure and Recombinant HIV-1 Strains Observed within Incident Infections during the HIV and Malaria Cohort Study Conducted in Kericho, Kenya, from 2003 to 2006.

Billings E, Sanders-Buell E, Bose M, Bradfield A, Lei E, Kijak GH, Arroyo MA, Kibaya RM, Scott PT, Wasunna MK, Sawe FK, Shaffer DN, Birx DL, McCutchan FE, Michael NL, Robb ML, Kim JH, Tovanabutra S - PLoS ONE (2015)

Bottom Line: This diversity and the resulting genetic distance between the observed strains will need to be addressed when vaccine immunogens are chosen.In consideration of current vaccine development efforts, the strains from these three studies were compared to five candidate vaccines (each of which are viral vectored, carrying inserts corresponding to parts of gag, pol, and envelope), which have been developed for possible use in sub-Saharan Africa.The sequence comparison between the observed strains and the candidate vaccines indicates that in the presence of diverse recombinants, a bivalent vaccine is more likely to provide T-cell epitope coverage than monovalent vaccines even when the inserts of the bivalent vaccine are not subtype-matched to the local epidemic.

View Article: PubMed Central - PubMed

Affiliation: United States Military HIV Research Program/Henry M. Jackson Foundation, Rockville, Maryland, United States of America.

ABSTRACT
Characterization of HIV-1 subtype diversity in regions where vaccine trials are conducted is critical for vaccine development and testing. This study describes the molecular epidemiology of HIV-1 within a tea-plantation community cohort in Kericho, Kenya. Sixty-three incident infections were ascertained in the HIV and Malaria Cohort Study conducted in Kericho from 2003 to 2006. HIV-1 strains from 58 of those individuals were full genome characterized and compared to two previous Kenyan studies describing 41 prevalent infections from a blood bank survey (1999-2000) and 21 infections from a higher-risk cohort containing a mix of incident and prevalent infections (2006). Among the 58 strains from the community cohort, 43.1% were pure subtypes (36.2% A1, 5.2% C, and 1.7% G) and 56.9% were inter-subtype recombinants (29.3% A1D, 8.6% A1CD, 6.9% A1A2D, 5.2% A1C, 3.4% A1A2CD, and 3.4% A2D). This diversity and the resulting genetic distance between the observed strains will need to be addressed when vaccine immunogens are chosen. In consideration of current vaccine development efforts, the strains from these three studies were compared to five candidate vaccines (each of which are viral vectored, carrying inserts corresponding to parts of gag, pol, and envelope), which have been developed for possible use in sub-Saharan Africa. The sequence comparison between the observed strains and the candidate vaccines indicates that in the presence of diverse recombinants, a bivalent vaccine is more likely to provide T-cell epitope coverage than monovalent vaccines even when the inserts of the bivalent vaccine are not subtype-matched to the local epidemic.

No MeSH data available.


Related in: MedlinePlus

Phylogenetic comparison of pure HIV-1 subtype sequences retrieved from prevalent and incident infections.Full genome sequences from prevalent HIV-1 subtype A1, C, D and G strains previously identified in 1999–2000 (green), a higher-risk (MSM and FSW) cohort identified in 2006 (blue), and the community cohort incident infections identified during this study in 2003–2006 (red), including relevant reference sequences (black) were used to construct a neighbor-joining tree. Bootstrap values at relevant nodes are shown. The scale bar indicates a genetic distance of 10%. Incident infection study participants 05KE851891V4 and 06KE795643V7 (*) are likely linked: pairwise genetic distance of 0.4% (SE 0.06%).
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pone.0135124.g002: Phylogenetic comparison of pure HIV-1 subtype sequences retrieved from prevalent and incident infections.Full genome sequences from prevalent HIV-1 subtype A1, C, D and G strains previously identified in 1999–2000 (green), a higher-risk (MSM and FSW) cohort identified in 2006 (blue), and the community cohort incident infections identified during this study in 2003–2006 (red), including relevant reference sequences (black) were used to construct a neighbor-joining tree. Bootstrap values at relevant nodes are shown. The scale bar indicates a genetic distance of 10%. Incident infection study participants 05KE851891V4 and 06KE795643V7 (*) are likely linked: pairwise genetic distance of 0.4% (SE 0.06%).

Mentions: A Neighbor Joining tree of pure subtype strains from the current and previous studies (Fig 2), shows that all pure subtype A1 virus identified in this incident cohort cluster with A1 reference sequences from East Africa. Among the pure A1 community cohort incident strains, 05KE851891V4 and 06KE795643V7 appear to be a directly genetic linked transmission pair with a pairwise distance of 0.4% (SE 0.06%). The demographic characteristics of the participants harboring those two strains show that they were a male and female living in a monogamous civil union; they were from the same ethnicity, same city, and the infection in the male was detected 6 months prior to the female. The subtype A1 sequences from this cohort are interspersed with the prevalent subtype A1 sequences identified during our previous blood bank survey as well as the A1 sequences identified during a more recent study (2006) involving a higher-risk cohort (MSM and FSW) from the Mombasa and Kilifi-Coast areas [17]. The three pure subtype C infections clustered with the single C virus identified during the prevalent infection (blood bank) study and reference subtype C strains from Botswana, Tanzania, Ethiopia, and India. The single subtype G virus (mostly found in West Africa) clustered with subtype G strains previously identified from Kenya [36] with a bootstrap value of 100%. This was confirmed via phylogenetic analysis using over 100 full-genome G and G-containing recombinant sequences (S1 Fig).


The Number and Complexity of Pure and Recombinant HIV-1 Strains Observed within Incident Infections during the HIV and Malaria Cohort Study Conducted in Kericho, Kenya, from 2003 to 2006.

Billings E, Sanders-Buell E, Bose M, Bradfield A, Lei E, Kijak GH, Arroyo MA, Kibaya RM, Scott PT, Wasunna MK, Sawe FK, Shaffer DN, Birx DL, McCutchan FE, Michael NL, Robb ML, Kim JH, Tovanabutra S - PLoS ONE (2015)

Phylogenetic comparison of pure HIV-1 subtype sequences retrieved from prevalent and incident infections.Full genome sequences from prevalent HIV-1 subtype A1, C, D and G strains previously identified in 1999–2000 (green), a higher-risk (MSM and FSW) cohort identified in 2006 (blue), and the community cohort incident infections identified during this study in 2003–2006 (red), including relevant reference sequences (black) were used to construct a neighbor-joining tree. Bootstrap values at relevant nodes are shown. The scale bar indicates a genetic distance of 10%. Incident infection study participants 05KE851891V4 and 06KE795643V7 (*) are likely linked: pairwise genetic distance of 0.4% (SE 0.06%).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543584&req=5

pone.0135124.g002: Phylogenetic comparison of pure HIV-1 subtype sequences retrieved from prevalent and incident infections.Full genome sequences from prevalent HIV-1 subtype A1, C, D and G strains previously identified in 1999–2000 (green), a higher-risk (MSM and FSW) cohort identified in 2006 (blue), and the community cohort incident infections identified during this study in 2003–2006 (red), including relevant reference sequences (black) were used to construct a neighbor-joining tree. Bootstrap values at relevant nodes are shown. The scale bar indicates a genetic distance of 10%. Incident infection study participants 05KE851891V4 and 06KE795643V7 (*) are likely linked: pairwise genetic distance of 0.4% (SE 0.06%).
Mentions: A Neighbor Joining tree of pure subtype strains from the current and previous studies (Fig 2), shows that all pure subtype A1 virus identified in this incident cohort cluster with A1 reference sequences from East Africa. Among the pure A1 community cohort incident strains, 05KE851891V4 and 06KE795643V7 appear to be a directly genetic linked transmission pair with a pairwise distance of 0.4% (SE 0.06%). The demographic characteristics of the participants harboring those two strains show that they were a male and female living in a monogamous civil union; they were from the same ethnicity, same city, and the infection in the male was detected 6 months prior to the female. The subtype A1 sequences from this cohort are interspersed with the prevalent subtype A1 sequences identified during our previous blood bank survey as well as the A1 sequences identified during a more recent study (2006) involving a higher-risk cohort (MSM and FSW) from the Mombasa and Kilifi-Coast areas [17]. The three pure subtype C infections clustered with the single C virus identified during the prevalent infection (blood bank) study and reference subtype C strains from Botswana, Tanzania, Ethiopia, and India. The single subtype G virus (mostly found in West Africa) clustered with subtype G strains previously identified from Kenya [36] with a bootstrap value of 100%. This was confirmed via phylogenetic analysis using over 100 full-genome G and G-containing recombinant sequences (S1 Fig).

Bottom Line: This diversity and the resulting genetic distance between the observed strains will need to be addressed when vaccine immunogens are chosen.In consideration of current vaccine development efforts, the strains from these three studies were compared to five candidate vaccines (each of which are viral vectored, carrying inserts corresponding to parts of gag, pol, and envelope), which have been developed for possible use in sub-Saharan Africa.The sequence comparison between the observed strains and the candidate vaccines indicates that in the presence of diverse recombinants, a bivalent vaccine is more likely to provide T-cell epitope coverage than monovalent vaccines even when the inserts of the bivalent vaccine are not subtype-matched to the local epidemic.

View Article: PubMed Central - PubMed

Affiliation: United States Military HIV Research Program/Henry M. Jackson Foundation, Rockville, Maryland, United States of America.

ABSTRACT
Characterization of HIV-1 subtype diversity in regions where vaccine trials are conducted is critical for vaccine development and testing. This study describes the molecular epidemiology of HIV-1 within a tea-plantation community cohort in Kericho, Kenya. Sixty-three incident infections were ascertained in the HIV and Malaria Cohort Study conducted in Kericho from 2003 to 2006. HIV-1 strains from 58 of those individuals were full genome characterized and compared to two previous Kenyan studies describing 41 prevalent infections from a blood bank survey (1999-2000) and 21 infections from a higher-risk cohort containing a mix of incident and prevalent infections (2006). Among the 58 strains from the community cohort, 43.1% were pure subtypes (36.2% A1, 5.2% C, and 1.7% G) and 56.9% were inter-subtype recombinants (29.3% A1D, 8.6% A1CD, 6.9% A1A2D, 5.2% A1C, 3.4% A1A2CD, and 3.4% A2D). This diversity and the resulting genetic distance between the observed strains will need to be addressed when vaccine immunogens are chosen. In consideration of current vaccine development efforts, the strains from these three studies were compared to five candidate vaccines (each of which are viral vectored, carrying inserts corresponding to parts of gag, pol, and envelope), which have been developed for possible use in sub-Saharan Africa. The sequence comparison between the observed strains and the candidate vaccines indicates that in the presence of diverse recombinants, a bivalent vaccine is more likely to provide T-cell epitope coverage than monovalent vaccines even when the inserts of the bivalent vaccine are not subtype-matched to the local epidemic.

No MeSH data available.


Related in: MedlinePlus