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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

Vaccine coverage of potential T-cell epitopes from the observed infections.Inserts from the candidate vaccines were analyzed for the proportion of nonamers that each of their respective immunogens covered within the infecting strains from the incident, higher-risk, and prevalent infection studies. For each immunogen, the epitope coverage comparisons were divided into the same pure and recombinant strain subsets used to generate Tables 1 and 2. The colored sections of each bar denote the proportion of coverage attributable to a perfect match (black) or mismatched (blue to gray) nonamer as indicted by the figure legend.
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pone.0135124.g005: Vaccine coverage of potential T-cell epitopes from the observed infections.Inserts from the candidate vaccines were analyzed for the proportion of nonamers that each of their respective immunogens covered within the infecting strains from the incident, higher-risk, and prevalent infection studies. For each immunogen, the epitope coverage comparisons were divided into the same pure and recombinant strain subsets used to generate Tables 1 and 2. The colored sections of each bar denote the proportion of coverage attributable to a perfect match (black) or mismatched (blue to gray) nonamer as indicted by the figure legend.

Mentions: Since the mosaic vaccine was designed to optimize the generation of T-cell epitopes, a comparison of the proportion of nonamers present in the infecting strains and overlapped by each vaccine was performed. The proportional coverage shown in Fig 5 represents the per-sequence average of nonamers present in the observed strains that were also present in the vaccine insert or inserts (as in the case of the bivalent mosaic vaccine). Further positional information is provided in Figures A-I in S1 File which include exact match nonamer positions, sequence logos [41] of the strain groups, and sequence positions of known CD8 epitopes for the viral protein regions used in these comparisons. By design [35], the mosaic vaccine (bivalent, containing subtypes B and C inserts) provides comparatively good nonamer coverage even within the recombinants; and while the Kenyan KEA insert provides better coverage among the pure strains, that advantage is lost once heterogeneity is introduced by the recombinants.


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)

Vaccine coverage of potential T-cell epitopes from the observed infections.Inserts from the candidate vaccines were analyzed for the proportion of nonamers that each of their respective immunogens covered within the infecting strains from the incident, higher-risk, and prevalent infection studies. For each immunogen, the epitope coverage comparisons were divided into the same pure and recombinant strain subsets used to generate Tables 1 and 2. The colored sections of each bar denote the proportion of coverage attributable to a perfect match (black) or mismatched (blue to gray) nonamer as indicted by the figure legend.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0135124.g005: Vaccine coverage of potential T-cell epitopes from the observed infections.Inserts from the candidate vaccines were analyzed for the proportion of nonamers that each of their respective immunogens covered within the infecting strains from the incident, higher-risk, and prevalent infection studies. For each immunogen, the epitope coverage comparisons were divided into the same pure and recombinant strain subsets used to generate Tables 1 and 2. The colored sections of each bar denote the proportion of coverage attributable to a perfect match (black) or mismatched (blue to gray) nonamer as indicted by the figure legend.
Mentions: Since the mosaic vaccine was designed to optimize the generation of T-cell epitopes, a comparison of the proportion of nonamers present in the infecting strains and overlapped by each vaccine was performed. The proportional coverage shown in Fig 5 represents the per-sequence average of nonamers present in the observed strains that were also present in the vaccine insert or inserts (as in the case of the bivalent mosaic vaccine). Further positional information is provided in Figures A-I in S1 File which include exact match nonamer positions, sequence logos [41] of the strain groups, and sequence positions of known CD8 epitopes for the viral protein regions used in these comparisons. By design [35], the mosaic vaccine (bivalent, containing subtypes B and C inserts) provides comparatively good nonamer coverage even within the recombinants; and while the Kenyan KEA insert provides better coverage among the pure strains, that advantage is lost once heterogeneity is introduced by the recombinants.

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