Britta Wahren Project

An effective HIV vaccine

Genetic vaccines have generated wide-spread interest for many applications, since DNA encoding a microbial gene results in in vivo expression of the desired gene, protein production and presentation as an endogenous foreign antigen. Due to these properties the polymorphic H LA system of humans can be targeted even with highly variable virus proteins, such as Human immunodeficiency virus (HIV), hepatitis C virus (HCV) or influenza.

HIV genes were constructed covering the highly variable sites of HIV envelopes and structural genes of Gag, subtypes A-E, the less variable parts of HIV regulatory genes and enzymes. Immunodominant non-neutralizing sequences were mutated, certain genes were changed to reduce toxicity and partial codon optimization was made to increase expression. Small size plasmids as well as divided doses of dominant versus subdominant genes together  show potent and broad immunological cross-reactivity. A boost with recombinant vaccinia-based vector including subtypes A and E genes effectively activated innate, humoral functional, helper cell, and cytotoxic responses, with memory retained up to over 1 year preclinically and over 3 years in the clinic. This vaccine prime boost schedule has resulted in a very high immunogenicity in a clinical phase 1 prophylactic studies (last publ Joachim et al 2016). We performed phase 2 clinical studies in Tanzania, Mocambique, Sweden and a pediatric immunoprophylactic study in children in Italy (Palma et al 2011-2015).

The DNA technology was also used to produce a targeting antibody directed against sensitive sites of the HIV-infected cell and virions. In a collaboration with US-based Immunomedics, the construction of this new class of anti-HIV agents was enabled using proprietary Dock-and-Lock (DNL) technology. The new molecules have three distinguished features. First, each comprises four copies of T20 (enfuvirtide), an approved peptide that prevents the virus from infecting immune cells. Second, the multiple peptides are linked to a humanized antibody without compromising their activity. Third, the incorporation of the peptides to the antibody confers additional benefits, such as enhanced anti-viral potency and improved pharmacokinetics. As a result, both infected cells and activated enhanced virus replication have been destroyed in cell culture and in vivo in infected animals. The concurrent plan is to prove viral decrease in monkeys, and to take the antiviral antibody to a small human trial. This constitutes a new class of drugs that significantly destroys the virus HIV as well as the infected cells. It has the (Human Immunodeficiency Virus), and may potentially eradicate the virus completely (Chang et al 2012-2016).


An interview with Britta Wahren October 2015

After receiving the KI Silver medal 2015 for outstanding achievement in the field of medical research, Britta Wahren talks about her research past and present

Research Rendezvous: an interview with Britta Wahren


Research networks

EAVI (European AIDS Vaccine Inititative)



Cancer och Allergi fonden


Involved in recent theses and examination works

Athina Kilpeläinen, mentor
PhD in Barcelona 2016- xxx

Lena Hansen, co-tutor with Karl Ljungberg
Strategies to enhance the immune response to HIV envelope
Read the Master´s thesis, University of Bergen     

Stefan Petkov, co-tutor
In vivo bioluminescence imaging in preclinical trials of genetic vaccines
Read the Lic thesis, KI                                                                                                 

Sofia Stenler, involved in minicircle synthesis, PI P Blomberg
Read the PhD thesis

David Hallengärd
Strategies to enhance the potency of HIV-1 DNA vaccines
    •    Read the Thesis (Pdf file, 1 Mb)

Rebecca Axelsson Robertson
Development of MHC class I African alleles and ex vivo detection of M.tuberculosis-reactive CD8+ T-cells
    •    Read the Thesis (Pdf file, 2 Mb)

Lindvi Gudmundsdotter
HIV-1 immune responses induced by natural infection or immunisation
    •    Read the Thesis (Pdf file, 2 Mb)

Andreas Boberg
Vaccination against drug-resistant HIV
    •    Read the Thesis (Pdf file, 1 Mb)

Erik Rollman

Susanne Johansson: Immunotherapy in cancer and HIV.
    •    Read the Thesis, KI


Andreas Bråve

Karl Ljungberg

Bartek Zuber

Anne Kjerrström



Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial.
Joachim A, Bauer A, Joseph S, Geldmacher C, Munseri P, Aboud S, et al
PLoS ONE 2016 ;11(5):e0155702

Early antiretroviral therapy in children perinatally infected with HIV: a unique opportunity to implement immunotherapeutic approaches to prolong viral remission.
Klein N, Palma P, Luzuriaga K, Pahwa S, Nastouli E, Gibb D, et al
Lancet Infect Dis 2015 Sep;15(9):1108-14

HIV-DNA Given with or without Intradermal Electroporation Is Safe and Highly Immunogenic in Healthy Swedish HIV-1 DNA/MVA Vaccinees: A Phase I Randomized Trial.
Nilsson C, Hejdeman B, Godoy-Ramirez K, Tecleab T, Scarlatti G, Bråve A, et al
PLoS ONE 2015 ;10(6):e0131748

Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.
Joachim A, Nilsson C, Aboud S, Bakari M, Lyamuya E, Robb M, et al
PLoS ONE 2015 ;10(4):e0118486

Short communication: HIV-1 Nef protein carries multiple epitopes suitable for induction of cellular immunity for an HIV vaccine in Africa.
Kilpeläinen A, Axelsson Robertson R, Leitner T, Sandström E, Maeurer M, Wahren B
AIDS Res. Hum. Retroviruses 2014 Nov;30(11):1065-71

Micro-minicircle Gene Therapy: Implications of Size on Fermentation, Complexation, Shearing Resistance, and Expression.
Stenler S, Wiklander O, Badal-Tejedor M, Turunen J, Nordin J, Hallengärd D, et al
Mol Ther Nucleic Acids 2014 Jan;2():e140

Therapeutic DNA vaccination of vertically HIV-infected children: report of the first pediatric randomised trial (PEDVAC).
Palma P, Romiti M, Montesano C, Santilli V, Mora N, Aquilani A, et al
PLoS ONE 2013 ;8(11):e79957

Broad and potent cellular and humoral immune responses after a second late HIV-modified vaccinia virus ankara vaccination in HIV-DNA-primed and HIV-modified vaccinia virus Ankara-boosted Swedish vaccinees.
Nilsson C, Godoy-Ramirez K, Hejdeman B, Bråve A, Gudmundsdotter L, Hallengärd D, et al
AIDS Res. Hum. Retroviruses 2014 Mar;30(3):299-311

A combination of intradermal jet-injection and electroporation overcomes in vivo dose restriction of DNA vaccines.
Hallengärd D, Bråve A, Isaguliants M, Blomberg P, Enger J, Stout R, et al
Genet Vaccines Ther 2012 Aug;10(1):5

A novel class of anti-HIV agents with multiple copies of enfuvirtide enhances inhibition of viral replication and cellular transmission in vitro.
Chang C, Hinkula J, Loo M, Falkeborn T, Li R, Cardillo T, et al
PLoS ONE 2012 ;7(7):e41235



Professor, senior

Britta Wahren

Telefon: 08-524 859 98
Enhet: Francesca Chiodi grupp



The viral diversity and latency of HIV-1 is likely to require a vaccine strategy that induces broad cellular and humoral anti-HIV-1 immunity. Our strategy is based on multiple HIV-1 DNA immunogens together with adjuvants, proteins and/or viral vector boosts. The vaccines are currently being tested in clinical HIV-1 phase I/II trials in Sweden, a trial in children in Italy and several phase II trials in Tanzania and Mocambique.

We investigate the short and long-term immunity in previously vaccinated HIV infected patients. Cells of the innate defense contribute to induction of specific immunity and to long-term prognosis of infection. Both phenotypic and functional changes in the NK-cell population are analyzed together with specific immunity. Antiviral therapy suppresses HIV replication but may select drug-resistant HIV variants. Therefore we will immunize patients against the most common drug-resistant variants of the virus.

Principle projects:

  • Genetic vaccines against HIV-1

MD, Foreign Adjunct Professor at MTC/KI Margaret A. Liu
Work: +46 (0)8 457 2630
Work: alt. +19252992559, +19
Fax: +46 (0)8 337272

Margaret A. Liu, who graduated from Harvard Medical School, has been Visiting professor at KI and is now Foreign Adjunct professor at MTC/KI. She has served as Senior Director at Merck Research Laboratories, Vice President of Vaccines Research and Gene Therapy at Chiron Corporation, Vice-Chairman of Transgene, and Senior Advisor in Vaccinology at the Bill and Melinda Gates Foundation and she is advisory for several international vaccine programs. She was the senior investigator of the efficacy of genetic vaccines in ground breaking studies on influenza, tumor viruses and HIV.

Gunnel Engström
Work: +46 (0)8 457 2691
Fax: +46 (0)8 337272

Gunnel has developed means for production and purification of DNA plasmids, and determined immunomodulatory effects of DNA as plasmids or as oligodeoxynucleotides. She is involved in clinical vaccine trials, for example the prophylactic vaccine project HIVIS where she is evaluating the bio-distribution of the vaccine plasmids in both preclinical and clinical settings. Issues regarding documentation for the Medical Products Agency (Läkemedelsverket) and reports on European union financed projects is handled through Gunnel.

  Postdoc Kristian Hallermalm

Kristian received his Ph.D. from Karolinska Institutet in 2004. His previous work includes studies on how to improve immune recognition of tumors and the identification of new mechanisms of tumor immune escape. In his current projects Kristian is developing new molecular adjuvants for DNA vaccination. Another part of his work concerns clinical evaluation of DNA vaccination strategies in humans.

Professor at Linköping University
Jorma Hinkula

Immunologist and virologist developed a mouse model system for HIV replication and production. He is now a professor at the Department of Molecular and Clinical Medicine, Linköping University. He is still intensively involved in studies of mucosal immunity and establishing new small animal models for HIV.

MD, PhD Bo Hejdeman
Bo Hejdeman at the South Hospital, Karolinska Institutet is a close collaborator in HIV vaccine studies.

MD, PhD, Professor Eric Sandström
Eric Sandström at the South Hospital, Karolinska Institutet is a close collaborator in HIV vaccine studies.

MD, PhD, senior Professor Gunnel Biberfeld
Gunnel Biberfeld is a close collaborator in HIV vaccine studies.