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Background There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine. Methods A total of 523 vaccinia-naive subjects were randomized to receive 2 vaccine doses, as lyophilized MVA given subcutaneously, liquid MVA given subcutaneously (liquid-SC group), or liquid MVA given intradermally (liquid-ID group) 28 days apart. For a subset of subjects, antibody-dependent cellular cytotoxicity (ADCC), interferon-γ release enzyme-linked immunospot (ELISPOT), and protein microarray antibody-binding assays were conducted. Protein microarray responses were assessed for correlations with plaque reduction neutralization titer (PRNT), enzyme-linked immunosorbent assay, ADCC, and ELISPOT results. Results MVA elicited significant microarray antibody responses to 15 of 224 antigens, mostly virion membrane proteins, at day 28 or 42, particularly WR113/D8L and WR101H3L. In the liquid-SC group, responses to 9 antigens, including WR113/D8L and WR101/H3L, correlated with PRNT results. Three were correlated in the liquid-ID group. No significant correlations were observed with ELISPOT responses. In the liquid-ID group, WR052/F13L, a membrane glycoprotein, correlated with ADCC responses. Conclusions MVA elicited antibodies to 15 vaccinia strain antigens representing virion membrane. Antibody responses to 2 proteins strongly increased and significantly correlated with increases in PRNT. Responses to these proteins are potential correlates of protection and may serve as immunogens for future vaccine development. Clinical Trials Registration NCT00914732.

Background. The ubiquitous human pathogens, herpes simplex virus (HSV)-1 and HSV-2, are distinct viral species that diverged approximately 6 million years ago. At least 4 small, ancient HSV-1 × HSV-2 interspecies recombination events have affected the HSV-2 genome, with recombinants and nonrecombinants at each locus circulating today. However, it is unknown whether interspecies recombination can affect other loci and whether new recombinants continue to be generated. Methods. Using 255 newly sequenced and 230 existing HSV genome sequences, we comprehensively assessed interspecies recombination in HSV. Results. Our findings show that the sizes and locations of interspecies recombination events in HSV-2 are significantly more variable than previously appreciated and that they can impact species-specific T-cell recognition of HSV. Conclusions. We describe 2 large (>5 kb) recombination events, one of which arose in its current host, demonstrating that interspecies recombination continues to occur today. These results raise concerns about the use of live-attenuated HSV-2 vaccines in high HSV-1 prevalence areas.

Here we present genomic and in vitro analyses of temporally separated episodes of herpes simplex virus type 1 (HSV-1) shedding by an HSV-1–seropositive and human immunodeficiency virus (HIV)/HSV-2–seronegative individual who has frequent recurrences of genital HSV-1. Using oligonucleotide enrichment, we compared viral genomes from uncultured swab specimens collected on different days and from distinct genital sites. We found that viral genomes from 7 swab specimens and 3 cultured specimens collected over a 4-month period from the same individual were 98.5% identical. We observed a >2-fold difference in the number of minority variants between swab specimens from lesions, swab specimens from nonlesion sites, and cultured specimens. This virus appeared distinct in its phylogenetic relationship to other strains, and it contained novel coding variations in 21 viral proteins. This included a truncation in the UL11 tegument protein, which is involved in viral egress and spread. Normal immune responses were identified, suggesting that unique viral genomic features may contribute to the recurrent genital infection that this participant experiences., This comparative viral genomics study of swab specimens and cultured specimens from a person with severe genital herpes simplex virus type 1 infection found that within-person diversity among minority variants in the viral population exists over a short period.

Background. Genital shedding of herpes simplex virus (HSV) type 2 occurs frequently. Anatomic patterns of genital HSV-2 reactivation have not been intensively studied. Methods. Four HSV-2-seropositive women with symptomatic genital herpes attended a clinic daily during a 30-day period. Daily samples were collected from 7 separate genital sites. Swab samples were assayed for HSV DNA by quantitative polymerase chain reaction. Anatomic sites of clinical HSV-2 recurrences were recorded. Results. HSV was detected on 44 (37%) of 120 days and from 136 (16%) of 840 swab samples. Lesions were documented on 35 (29%) of 120 days. HSV was detected at >1 anatomic site on 25 (57%) of 44 days with HSV shedding (median, 2 sites; range, 1-7), with HSV detected bilaterally on 20 (80%) of the 25 days. The presence of a lesion was significantly associated with detectable HSV from any genital site (incident rate ratio [IRR], 5.41; 95% confidence interval [CI], 1.24-23.50; P = .02) and with the number of positive sites (IRR, 1.19; 95% CI, 1. 01-1.40; P = .03). The maximum HSV copy number detected was associated with the number of positive sites (IRR, 1.62; 95% CI, 1.44-1.82; P

The immunogenicity of a high hemagglutinin (HA) dose or a second dose of influenza vaccine in human immunodeficiency virus (HIV)-infected individuals has not been fully explored.One hundered ninety-two HIV-infected individuals aged 18-64 years were stratified by CD4 cell count (200 cells/mL or ≥200 cells/mL) and randomized to receive 2 doses of 15 μg or 30 μg HA 2009 H1N1 vaccine 21 days apart. Hemagglutination inhibition (HAI) and microneutralization (MN) antibodies were measured on days 0, 10, 21, 31, 42, and 201.Recipients of 30 μg HA had significantly higher HAI geometric mean titers (GMTs), compared with recipients of 15 μg HA on days 10 (139.0 vs 51.9; P = .01), 21 (106.7 vs 51.9; P = .001), and 31 (130.0 vs 73.7; P = .03) but not on days 42 (91.8 vs 61.6; P = .11) and 201 (43.0 vs 27.0; P = .08). When analyzed by CD4 cell count stratum, HAI GMTs were significantly higher among 30 μg HA recipients than among 15 μg HA in the CD4 cell count200 cells/mL stratum on days 21 and 31 and the MN GMTs on days 10, 21, 31, and 42 (P.05). In the CD4 cell count ≥200 cells/mL stratum, MN GMTs were significantly higher among recipients of 30 μg HA than among recipients of 15 μg HA on day 10 (P = .03).Increasing the HA dose of the 2009 H1N1 vaccine improves the vaccine's immunogenicity in HIV-infected individuals.NCT00992433.

Primary genital herpes simplex virus (HSV) infection is commonly associated with systemic symptoms. A systematic evaluation of HSV viremia during primary genital infection has not been performed previously. Plasma samples from adults with a first clinical episode of genital HSV infection were assayed for HSV DNA by polymerase chain reaction. One hundred sixty-four adults had confirmed primary genital HSV infection. Of these, 40 (24%) had HSV DNA detected in plasma. Thirty-seven (93%) of 40 were infected with HSV-2. Viremic participants were more likely to be women, compared with aviremic participants (83% vs. 61%; P = .01). Viremia was detected more frequently and at a higher number of copies per milliliter early in infection. We conclude that HSV viremia during primary genital HSV infection is common, especially among women.