HIV-exposed uninfected infants show robust memory B cell responses in spite of a delayed accumulation of memory B cells: An observational study in the first two years of life.

Background Improved HIV care has led to an increase in the number of HIV-exposed uninfected (HEU) infants born to HIV infected women. Although uninfected, these infants experience increased morbidity and mortality. One explanation may be that their developing immune system is altered by HIV-exposure predisposing them to increased post-natal infections. Methods We explored the impact of HIV-exposure on the B-cell compartment by determining the B-cell subset distribution, the frequency of common vaccine antigen-specific memory B cells (MBCs) and their respective antibody levels in HEU and HIV-unexposed uninfected (HUU) infants born to uninfected mothers, using flow cytometry, B-cell ELISPOT and ELISA, respectively, during the first two years of life. Results For the majority of the B-cell subsets there were no differences between HEU and HUU infants. However, HIV exposure was associated with a lower proportion of B cells in general and specifically MBCs, largely due to a lower proportion of unswitched memory B cells. This reduction was maintained even after correcting for age. These phenotypic differences in the MBC compartment did not affect the ability of HEU infants to generate recall responses to previously encountered antigens, or reduce the antigen-specific antibody levels at 18 months of life. Conclusions Although HIV-exposure was associated with a transient reduction in the proportion of MBCs, we found that the ability of HEUs to mount robust MBC and serological responses was unaffected

Body composition and maximum alactic anaerobic performance during a one month stay at high altitude

Prolonged altitude exposure usually leads to considerable weight loss of which a large part is from muscle tissue. This loss reduces maximum alactic anaerobic muscle power. It was hypothesized that most of the weight loss may simply be the result of malnutrition due to lack of palatable food in an uncomfortable environment. To test this hypothesis eight healthy male subjects (age 33.7 \ub1 4.6 S.C. yr), well acclimatized to prevent symptoms of acute mountain sickness, were exposed for 4 weeks to an altitude of 5050 m with access to a large choice of palatable food in comfortable conditions. Body weight (with a scale), body composition (from skinfolds), arm muscle plus bone cross-sectional area (Am + b) and muscle plus bone leg volume (Vm + b) (from skinfolds and circumferences), maximum voluntary contraction force of the elbow flexors (MVC, with a load cell) and maximum jumping height (Hmax, on a platform) were measured before departure (SL) and in the first (ALT1), second (ALT2) and fourth week (ALT4) of their altitude sojourn. Three-day dietary records were obtained at SL and at ALT4. Body mass had decreased significantly at ALT2 (-3.8%) and at ALT4 (-4.6%) likely reflecting changes in body water homeostasis. No changes were found in \ufat, Am + b, Vm + b, MVC or Hmax. Average dietary intake at SL was 8.96 \ub1 1.45 MJ and had increased to 13.59 \ub1 3.07 MJ at ALT4. In conclusion, up to an altitude of 5050 m loss of body mass from fat and muscle tissue, and hence impairment of maximum anaerobic muscle power (alactic) appears to be avoidable by food intake matched to energy expenditure. The latter may be achieved simply by proper acclimatization, sufficient comfort and availability of palatable food

Single cytokine CD4 and CD8 T-cell responses to polyclonal stimulation with SEB.

<p>The magnitude of CD4 (A) and CD8 (B) T-cell IFN-γ, IL-2, TNF-α or any cytokine (Any) responses following short-term stimulation with SEB in HIV-unexposed (HU) and HIV- exposed uninfected (HEU) infants in month 3 (M3) and month 12 (M12) age groups. The black line is the median frequency of T-cells expressing the indicated cytokine or any cytokine. The Mann Whitney U test was used to assess differences between the two groups.</p

Single cytokine CD4 and CD8 T-cell responses to vaccine antigens.

<p>The magnitude of CD4 (A) and CD8 (B) T-cell IFN-γ, IL-2, TNF-α or any cytokine (Any) responses following short term stimulation with PPD in HIV-unexposed (HU) and HIV-exposed uninfected (HEU) infants in month 3 (M3) and month 12 (M12) age groups. Similarly, the magnitude of cytokine responses to TT are shown in (C) for CD4 T-cells only. The horizontal black line is the median frequency of T-cells expressing the indicated cytokine or any cytokine. The Mann Whitney U test was used to assess differences between the two groups.</p

Memory phenotype of vaccine antigen responsive CD4 T-cells.

<p>(A) Analysis of the memory phenotype of CD4 T-cells that express any cytokine (IFN-γ, IL-2 or TNF-α) in response to short-term stimulation with PPD. (B) A similar analysis was carried out following short-term stimulation with TT. Comparisons were made between HIV-unexposed (HU) and HIV-exposed uninfected (HEU) infants at month 3 (M3) and month 12 (M12) age groups. The horizontal line in the box and whisker plots is the median percentage of cytokine secreting T-cells with a particular surface memory phenotype, the box is the interquartile range and the whiskers the 10^th and 90^th percentiles. T_CM: central memory, T_EM: effector memory, T_EMRA: effector memory that re-express CD45RA. The Mann Whitney U test was used to assess differences between the two groups.</p

Polyfunctional CD4 T-cell responses to stimulation with vaccine antigens and following polyclonal stimulation with SEB.

<p>(A) CD4 T-cells expressing combinations of IFN-γ, IL-2 and/or TNF-α were analysed using Boolean gating following short-term stimulation with PPD in HIV-unexposed (HU) and HIV-exposed uninfected (HEU) infants in the month 3 (M3) age group. (B) A similar analysis is shown assessing TT responses in the month 12 (M12) age group. Similarly, polyfunctional SEB responses in M3 (C) and M12 (D) age groups are shown. The black line is the median frequency of T cells expressing the indicated cytokine combination, the box is the interquartile range and the whiskers the 10^th and 90^th percentiles. The Mann Whitney U test was used to assess differences between the two groups.</p

Genomic epidemiology of SARS-CoV-2 in Seychelles, 2020–2021

Seychelles, an archipelago of 155 islands in the Indian Ocean, had confirmed 24,788 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the 31st of December 2021. The first SARS-CoV-2 cases in Seychelles were reported on the 14th of March 2020, but cases remained low until January 2021, when a surge was observed. Here, we investigated the potential drivers of the surge by genomic analysis of 1056 SARS-CoV-2 positive samples collected in Seychelles between 14 March 2020 and 31 December 2021. The Seychelles genomes were classified into 32 Pango lineages, 1042 of which fell within four variants of concern, i.e., Alpha, Beta, Delta and Omicron. Sporadic cases of SARS-CoV-2 detected in Seychelles in 2020 were mainly of lineage B.1 (lineage predominantly observed in Europe) but this lineage was rapidly replaced by Beta variant starting January 2021, and which was also subsequently replaced by the Delta variant in May 2021 that dominated till November 2021 when Omicron cases were identified. Using the ancestral state reconstruction approach, we estimated that at least 78 independent SARS-CoV-2 introduction events occurred in Seychelles during the study period. The majority of viral introductions into Seychelles occurred in 2021, despite substantial COVID-19 restrictions in place during this period. We conclude that the surge of SARS-CoV-2 cases in Seychelles in January 2021 was primarily due to the introduction of more transmissible SARS-CoV-2 variants into the islands