Huw Davies

Cutting Edge: Long-Term B Cell Memory in Humans after Smallpox Vaccination

Memory B cells are a central component of humoral immunity, and yet little is known about their longevity in humans. Immune memory after smallpox vaccination (DryVax) is a valuable benchmark for understanding the longevity of B cell memory in the absence of re-exposure to Ag. In this study, we demonstrate that smallpox vaccine-specific memory B cells last for >50 years in immunized individuals. Virus-specific memory B cells initially declined postimmunization, but then reached a plateau ∼10-fold lower than peak and were stably maintained for >50 years after vaccination at a frequency of ∼0.1% of total circulating IgG+ B cells. These persisting memory B cells were functional and able to mount a robust anamnestic Ab response upon revaccination. Additionally, virus-specific CD4+ T cells were detected decades after vaccination. These data show that immunological memory to DryVax vaccine is long-lived and may contribute to protection against smallpox.

Definition of linear antigenic regions of the HPV16 L1 capsid protein using synthetic virion-like particles

Mice of three haplotypes (H-2d, H-2b, and H-2d/b) were immunized with synthetic HPV16 virus-like particles (VLPs), produced using a vaccinia virus doubly recombinant for the L1 and L2 proteins of HPV16. The resultant anti-VLP antisera recognized HPV16 capsids by ELISA assay and baculovirus recombinant HPV16 L1 and L2 protein on immunoblot. Overlapping peptides corresponding to the HPV16 L1 amino acid sequence were used to define the immunoreactive regions of the L1 protein. The majority of the L1 peptides were reactive with IgG from the mice immunized with the synthetic HPV16 capsids. A computer algorithm predicted seven B epitopes in HPV16 L1, five of which lay within peptides strongly reactive with the murine antisera. The murine anti-VLP antisera failed to react with the two peptides recognized by anti-HPV16L1 monoclonal antibodies raised by others against recombinant L1 fusion protein. We conclude that the immunoreactive epitopes of HPV16 defined using virus-like particles differ significantly from those defined using recombinant HPV16 L1 fusion proteins, which implies that such fusion proteins may not be the antigens to look for HPV16L1 specific immune responses in HPV-infected patients.

Wellington's First Command: The Political and Military Campaign Against Dhoondiah Vagh, February–September 1800

Wellingtons first independent command has been seen as a short, but intense, ‘baptism of fire’ in which the young Lieutenant-Colonel Arthur Wellesley commanded a small force against the insurgent, or ‘freebooter’, Dhoondiah Vagh. New evidence presented here, however, demonstrates that the three-month military campaign was preceded by several months of political negotiation and intelligence gathering designed to isolate Dhoondiah and starve him of sanctuary, support and sustenance. As a result, the campaign was much more complex than previously thought, and demonstrates important lessons about British imperial expansion in the region at the beginning of the nineteenth century, on the nature of British authority in India, and on the opening stages of the military career of the future Duke of Wellington.

Integration of strategic and operational intelligence during the Peninsular war

Wellington is well known for his understanding of the importance of intelligence, but so far history has recorded that he presided over a one-man intelligence department, himself being the only analyst of what proved to be a massive quantity of raw information. New research highlighted in this article reveals that this has been an inaccurate interpretation. The British government also acted to establish a civilian network of correspondents and agents communicating with the British ambassadors to Spain and Portugal. Wellingtons main priority was to integrate the ‘strategic intelligence’ collected by government agents with his own ‘operational intelligence’. Instead, analysis was conducted more by Wellingtons subordinates in the field, applying their personal localized expertise to the information they received. In this way, an early and primitive form of the staff system later developed by the Prussians was created in the Peninsular War.

Intelligence and the Art of Command, 1799–1945

Although it refers to warfare in Roman times, Shakespeare’s famous statement nevertheless teaches a timeless lesson, both for operational and military, and strategic and political decision-makers. In making the comment, Enobarbus, Mark Anthony’s faithful advisor and soldier, is referring to his friend’s mistaken belief that he can fight Octavius Caesar, Anthony’s challenger for the seat of power in Rome, at sea. All advice and intelligence suggests the contrary, that although Anthony has Cleopatra’s vast fleet at his disposal, it is still no match for Octavius’s. Anthony is much stronger on land, but his valour, and his mistaken belief in his own invincibility, prevents him from understanding this. Subsequently, Anthony is defeated at sea. Anthony’s valour, or his preconceived belief in his own invulnerability, prevented him from acting on intelligence which predicted his almost certain defeat. Strategically, of course, the same intelligence indicated that war with Octavius was unnecessary and foolish. Not only was Anthony militarily and strategically weaker than Octavius, but the war was tearing apart the Roman Empire, making the victor weaker. Despite this, the war occurred, and this was due to political imperatives: Octavius had attacked Anthony’s ally, Sextus Pompeiius. As a result, despite the debilitating nature of the conflict, the primacy of the political imperative made it inevitable. The remainder of the story is typically Shakespearean. Suspecting Cleopatra’s betrayal, Anthony determines to kill his lover. Scared for her life, Cleopatra sends word she has killed herself in grief. Anthony, stricken by the news, attempts suicide, only to be reconciled with his lover moments before his death. Captured by Caesar, Cleopatra commits suicide herself with the bite of a poison asp. The story would have been much rosier, but infinitely less interesting, if Anthony had only listened to reason rather than valour. Such is the case with countless military defeats across history, and military

The Influence of Intelligence on Wellington's Art of Command

Wellingtons use of intelligence developed over the course of his military career. Eventually, he became a master of information exploitation, incorporating intelligence analysis into not only his own command practices, but those of his subordinates as well. By the close of the Peninsular War, military intelligence played a major role in achieving victory over the French. This article analyses the development of Wellingtons use and understanding of intelligence throughout his military career, comparing his early ‘command apprenticeship’ in India in 1800, where he developed an understanding of the importance of intelligence, which he subsequently exported to, and developed, in the Iberian Peninsula.

Wellington's use of deception tactics in the Peninsular War

Abstract Wellingtons use of intelligence developed throughout his military career. Arguably, his experiences in India taught him the importance of intelligence, but it was during the Peninsular War that he honed his analytical techniques. As the war progressed, he developed sophisticated methods for the integration of strategic intelligence – largely gathered by civilian agents – with operational intelligence – collected by military personnel. This allowed him to develop operational conceptualisation, which in turn contributed to the successes he achieved over the French forces in Iberia. However, more than anything, it was his considered use of intelligence, combined with intricate deception operations in the latter stages of the conflict, which deprived the French of reliable intelligence on his own movements, and demonstrated his understanding of the importance of intelligence. This article investigates Wellingtons increasing awareness of the importance of intelligence and deception during the Peninsular War.