The prospect of preventing HIV infection with broadly neutralising monoclonal antibodies (bNAbs) has generated unprecedented enthusiasm in the scientific community and hope among people living with HIV around the world. HIV bNAbs could be a game changer in the prevention of HIV acquisition. Some of these bNAbs are being tested in early phase clinical trials, and the debate is now about the priorities for strategic large-scale efficacy trials. The prevailing view is that only a fixed combination of at least three bNAbs could prevent HIV, regardless of target populations or routes of transmission. We propose an alternative strategy consisting of evaluating the tolerability and efficacy of one or two bNAbs cocktails tailored to different target populations and indications. The rationale for this alternative strategy is based on ethical, pathophysiological and practical facts and is illustrated by the possibility of preventing HIV transmission through breastfeeding in high incidence/prevalence areas such as southern Africa. There is a prospect of eliminating paediatric HIV acquisition through breastfeeding by using single/dual long-acting bNAb regimens.

Abstract ( n=254/250 words)   Background: The Janssen-Ad26.COV2.S vaccine is authorised for use in several countries with more than 30 million doses administered. Mild and severe allergic adverse events following immunisation(AEFI) have been reported. The aim of this report is to detail allergic reactions reported during the Sisonke phase 3B study in South Africa. Methods: A single-dose of the Ad26.COV2.S vaccine was administered to 477234 South African Healthcare Workers between 17 February and 17 May 2021. Monitoring of adverse events used a combination of passive reporting and active case finding. Telephonic contact was attempted for all adverse events reported as “allergy”. Anaphylaxis adjudication was performed using the Brighton Collaboration (BCC) and NIAID case definitions.  Results: A large cohort of South African healthcare workers received the Ad26.COV2.S vaccination. Only 250(0.052%) patients reported any allergic-type reaction(less than 1 in 2000), with four cases of adjudicated anaphylaxis (BCC level 1, n=3)(prevalence of 8.4 per million doses). All anaphylaxis cases had a prior history of drug or vaccine-associated anaphylaxis. Cutaneous allergic reactions were the commonest non-anaphylatic reactions and included: self-limiting, transient/localised rashes requiring no healthcare contact(n=91); or isolated urticaria and/or angioedema[n=70 median  onset 48(IQR 11.5-120) hours post vaccination] that necessitated healthcare contact(81%), antihistamine(63%), and/or systemic/topical corticosteroid(16%). All immediate (including adjudicated anaphylaxis) and the majority of delayed AEFI(65/69) cases resolved completely.   Conclusions: Allergic AEFI are rare following a single-dose of Ad26.COV with complete resolution in  all cases of anaphylaxis. Though rare, isolated, delayed onset urticaria and/or angioedema was the commonest allergic AEFI requiring treatment, with nearly half occurring in participants without known atopic disease.   Keywords: allergic reaction, anaphylaxis, COVID19 adenovirus vaccine; Janssen-Ad26.COV2.S vaccine, urticaria